The movie starts in a peaceful suburban neighborhood on a bright morning. Lenny Feder (Adam Sandler) wakes up next to his wife Roxanne (Salma Hayek). He turns to his side and finds a deer standing by the bed. Lenny whispers to Roxanne to open the window, and as she tells him to open it himself, she sees the deer and screams, frightening it and causing it to pee all over Lenny. The deer starts running around the house with Roxanne's bras on its antlers, peeing on the oldest Feder kid Greg (Jake Goldberg) before it runs to the kitchen. Lenny notices that the deer is attracted to his daughter Becky's (Alexys Nycole Sanchez) stuffed monkey Mr. Gigglesworth, so Lenny grabs it and tosses it out the front door as the deer mauls the doll to Becky's horror.
Cut to the Lamonsoff household, where Sally (Maria Bello) is teaching her son Bean (Frank and Morgan Gingerich) math. He is absolutely horrible at it, and neither Sally nor her husband Eric (Kevin James) are helping by encouraging his wrong answers. Their daughter Donna (Ada-Nicole Sanger) comes downstairs with ridiculous boots that light up and are bedazzled.
Kurt Mackenzie (Chris Rock) is with his wife Deanne (Maya Rudolph) and their kids Andre (Nadji Jeter) and Charlotte (China Anne McClain), along their infant son Ronnie (Kaleo Elam) who has a thick diaper on. Thinking it's full of poop, Deanne is stunned to find a box with a necklace in it. Turns out Kurt remembered their anniversary and Deanne forgot.
Marcus Higgins (David Spade) is at a train station waiting for a son he never knew he had from a woman he barely remembers. Out of the train comes a large and tattooed guy named Braden (Alexander Ludwig), who is indeed Marcus's kid. Marcus hands him a teddy bear, which Braden quickly decapitates with his switchblade.
As Roxanne is leaving for work, she mentions to Lenny that she enjoys having moved to the suburbs and ponders the thought of having a fourth kid, which Lenny is not particularly pleased with. As she leaves, he has a talk with his kids and learns that Greg has a crush on a girl named Nancy Arbuckle. Bean and Becky ride their bikes to school as a bus comes for Greg and Keithie (Cameron Boyce), but finds it funny when an old friend named Nick (Nick Swardson) is driving the bus. He is inebriated and just an overall colossal idiot, so Lenny takes over and drives his kids and other kids to school while also picking up Kurt. Kurt suggests throwing a party at Lenny's house that evening, while at the same time, a large bully is making fun of Donna's shoes, so when Keithie steps in to defend her, the bully threatens to harm him when Lenny isn't looking. After dropping the kids off at school, the guys pick Eric up and go to K-Mart.
Roxanne goes to her fashion store and learns from one of her employees Penny (Cheri Oteri) that she used to be Lenny's girlfriend. She clearly hasn't gotten over him and still keeps a note on her person that they wrote each other, which is nothing more than a question as to how her hair looks. Roxanne later goes to a fitness class with Sally and Deanne. Initially, a very creepy janitor (Jon Lovitz) instructs the ladies for his own pleasure before a handsome instructor comes in. The ladies all find him hot but are disappointed when he tells them he's gay.
At K-Mart, Nick takes his pants and shirt off and tries to nap in one of the beds. He's taken out and then starts to shit in one of the toilets. Meanwhile, Lenny, Kurt, and Eric find Marcus looking at a big knife to defend himself against his son. Throughout their time there, they run into Robideaux (Jonathan Loughran), one of the rivals from the first film, and Lenny mentions the bully on the bus and remembers a kid named Tommy Cavanaugh that used to harass him. They also find an old schoolmate named Malcolm (Tim Meadows), whom they mock for his bald spot. On their way out, they run into two old friends who are now cops - Officers Fluzoo (Shaquille O'Neal) and Dante (Peter Dante). They're both crazy and they escort Lenny and his friends to Becky's elementary school for a dance recital. The guys are into the show because of Becky's really hot dance teacher (April Rose). After the show, Roxanne learns that Lenny and the guys were talking about the party, and as they talk to the dance teacher, her boyfriend comes in, and it turns out to be Tommy Cavanaugh (Steve Austin). He heard that Lenny was talking about kicking his ass, and Lenny fearfully denies all of it. He and Eric take their families to get ice cream and they find Dickie Bailey (Colin Quinn), the leader of the rivals. He tells them that the soft serve machine is broken, and when Marcus tells him how to fix it, they mock him as he is standing in a position that makes it look like the machine is squirting chocolate ice cream through his legs.
For the kids at school, Greg and Andre meet Braden since Marcus made him attend school even though it's the last day. Meanwhile, Donna and Charlotte meet Malcolm's wannabe gangsta son Bumpty (Kamil McFadden), who is attracted to Charlotte. As the school year comes to an end, Braden invites Greg and Andre to sneak into an area where college kids are partying by a cliff in the lake. The boys pretend to be college students to party with them when they spot many hot girls there. At the same time, Lenny, Eric, Kurt, and Marcus come into the same spot, not seeing the boys. They reminisce about their time hanging out in the lake, until they are spotted by a group of frat boys led by Andy (Taylor Lautner). The boys mock the men and tell them to jump off the cliff naked into the lake. They all do so, hitting the water hard and ending with Eric landing on Marcus. Braden sees Marcus and is pissed at him after he was originally told that he was working at a soup kitchen.
The men go back to their van to find that the frat boys slashed their tires. They take the van to Eric's auto repair shop, and they get Marcus to fit in a large tire so he can roll all the way downtown and into Fluzoo. It also turns out they've arrested Braden for vandalism.
The frat boys discover that their house has been vandalized, with loads of toilet paper hanging all over the place and graffiti sprayed everywhere. They all swear to get revenge on the men, and then begin attacking each other out of fury.
Throughout the rest of the day, we see the guys partaking in various activities prior to the party. Lenny teaches Keithie to play football, and he turns out to be very skilled, attracting the attention of high school football players and their coach, but the glory is cut short when Lenny accidentally trips and falls on Keithie, breaking his leg, which pisses Roxanne off since she never wanted him to try out for football. Eric hangs out with his mother watching soap operas instead of attending to some appointment that Sally wanted him to go to. They make up and go to a car wash where male cheerleaders get all up on the car and wash it. Kurt has Andre go for his road test with yet another rival, Wiley (Steve Buscemi), as Kurt, who works for a cable company, goes to deliver cable to his obnoxious mother-in-law, only to leave a "sorry we missed you" note when she goes to the bathroom. Marcus also tries to connect with Braden, who isn't happy with how he calls his mother "Hiccups McGee" (Marcus only remembers her because she had the hiccups when they made out).
The time for the party comes, and the Feders have an 80's theme going on. Lenny gets into an argument with Roxanne over having another kid, and she reveals that she is pregnant. He laments to the guys about having a fourth child, as well as the fact that they were mocked by a younger generation of guys. They think they've gotten way past their prime, but the other guys think they've still got some life in them.
More guests arrive, with some looking like Prince (Kurt), Meatloaf (Eric), Hall & Oates (Marcus and Braden), Bruce Springsteen (Lenny), and etc. More antics occur, such as Penny, who turns out to be Wiley's wife, trying to get Lenny to meet with her again and engage in an affair. Bumpty hangs out with Charlotte and proves to be a really lame person. Greg spots Nancy Arbuckle (Halston Sage), who is dressed as Pat Benatar. Bean proves to be skilled at the piano. The gay fitness instructor shows up dressed as Indiana Jones and fixes Becky's stuffed monkey. Tommy Cavanaugh shows up, and after Lenny sees the school bully messing with Keithie again, he decides to finally get Tommy to apologize for what he's done. He challenges him to a fight, but Tommy stops by faking a fear of Lenny and telling him to play along so they can let bygones be bygones.
Everything appears to be going great until the frat boys and their college friends show up as an army. They mock Lenny and everybody else for swimming in their spot, but Dickie stands up for Lenny after realizing he left his Hollywood agent job to return to his hometown because he loved it. Everybody else stands by Lenny and his friends. The frat boys challenge everybody at the party to a fight, and a large brawl ensues. The frat boys are all beaten up, and in the process, relationships are formed - Greg hooks up with Nancy, the bully befriends Keithie after he saves him from a frat boy, and Fluzoo even throws one frat boy over the house. Lenny tries to fight off Andy, but he is too tough for him. Becky saves him by giving Andy her stuffed monkey, which attracts the deer from earlier, and he jumps Andy and attacks him.
After the party, Lenny and his friends, now joined by Dickie, gather at Eric's mom's house for dinner. They look over an old photo album and reminisce. When the subject of Lenny's fourth child comes up, Eric's mom says this is something he should be looking forward to. Lenny goes home that night and accepts that he will be having another kid. He proceeds to make love to Roxanne again, but not before burping, snorting, and farting altogether (seriously).
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