NOTE: This spoiler was submitted by Jeremy

The film starts with divorced nurse Maura Ellis (Amy Poehler) coming across a man on the street that she believes to be homeless. She wants to help him out, only to watch as he and his friends enter a truck to return to work, making her feel embarrassed. When she gets home, Maura has a Skype chat with her parents Bucky (James Brolin) and Deanna (Dianne Wiest). They drop the news to her that they are planning to sell their old home, to Maura's disappointment. Her parents want her to break the news to her sister, knowing she wouldn't take it well if their parents told her.

Maura's sister Kate (Tina Fey) works in her home as a stylist. She tends to a customer named Phil (Chris Parnell), trying to do his eyebrows in time for a date, only to be adding something that causes his eyebrows to slowly burn off. Kate is visited by her daughter Haley (Madison Davenport), who intends to stay with her. Kate admits that she got fired from her last job for flipping out on her boss, and Haley leaves quickly after seeing that her mom is a mess, deciding to stay with a friend.

Kate goes down to Florida and meets up with Maura. Kate plans to move back into the house with Maura until they can both get back on their feet. On their way home, they stop at the liquor store and run into a repugnant old classmate named Dave (John Leguizamo), who tries to hit on both women with no luck. They both go home to discover the "sold" sign in front of their house when they pull up to it. Kate throws a tantrum on the front lawn, and Maura is surprised since she didn't realize their parents already sold the house.. Their parents have cleaned out almost the entire house, except for the sisters' old bedroom. Bucky and Deanna ask them to clean it out for the new owners.

The ladies go through their old stuff, including their diaries. After reading a bunch of old entries, Kate says she feels bad that Maura never got to have her "big night" in their bedroom. Kate wants to throw a party, and although Maura is initially hesitant, she comes to agree to the idea.

Maura and Kate begin their mission to throw one last epic party. They look up their old graduating class and decide which ones to invite, specifically leaving out Kate's nemesis Brinda (Maya Rudolph) and a dorky classmate named Alex (Bobby Moynihan), who tries way too hard to be funny. They buy a bunch of party supplies, only to run into Brinda at the supermarket, where she is clearly upset over not getting an invitation to the party. The sisters come across the new owners, the Geernts (Santino Fontana and Britt Lower). The ladies exchange banter with them and mock them for wanting to paint the steps of the house blue and for wanting to take down their old "sister tree". They go out and shop for new outfits as well.

The sisters get their nails done, and Maura, compassionate to a fault, invites the stylist Vicky, aka Hae-Woo (Greta Lee) and her friends to the party. While at the salon, Maura notices a "hiring now" sign and gets Kate to go ask for a job. The manager looks at Kate's bad nail polish job and turns her away, but she makes him appear as though he gave her a job to convince Maura. The last thing they need to do is to cancel dinner with the parents. They go to the retirement resort where they're staying and discover they've caught them in the middle of sex, to everyone's horror.

Kate drives Maura by the house of James (Ike Barinholtz), a guy that caught Maura's eye. She awkwardly invites him to the party, which he accepts. When they get home, Maura offers to give Kate a loan since she's supposedly turning her life around. She also asks Kate if she can be the "party mom" that night and not drink so Maura can get drunk and let loose. Kate reluctantly agrees.

Night falls, and the sisters get ready for guests to arrive. Their old classmates quickly arrive, including Alex, whom Maura invited out of guilt. He starts off by quickly cracking terrible jokes. More guests arrive, but they only mingle and don't actually enjoy themselves. Things pick up when a group of lesbians arrive with their own DJ and get the party going. Meanwhile, Brinda and her friends are watching "Game of Thrones", but the other two friends want to go to the party.

Brinda shows up to the party with her friends, but Kate kicks out Brinda and lets the friends stay. She then asks Dave if he can call up his drug dealer and bring some good stuff. Hae-Woo and her friends show up in revealing outfits to bring youthful energy to the party, which is mostly comprised of older couples...and Alex. Brinda tries to get in again, but Kate throws her out for good. Brinda decides to get back by taking blue paint and pouring it into the water pumps, turning the pool water (and the people in it) a dark shade of blue.

Dave's drug dealer Pazuzu (John Cena) shows up with a case stocked up with every drug known to man (including birth control pills and Flintstones gummies). Maura and Kate buy some joints and a bag of cocaine, which Maura hides in her bag, which she hides in her cupboard. Unfortunately, Alex, who is acting out "Scarface", decides to get too into character and snorts half the bag all at once, causing him to wreak havoc around the house.

Maura finds James and smokes a joint with him in the attic. Together, they talk about each other and their personal fears. James says he recently lost weight to build self-confidence, while Maura thinks she is too boring. One of her favorite songs comes on, and she starts to dance, only to walk over the attic floor and have her fall through and get partially stuck. James pulls her out, but the floor starts to shake beneath them. They run and end up falling through the ceiling of her bedroom, covered in piles of dust. Still, the two decide to get intimate, after James tries to fix the ceiling. However, Maura lights a Garfield candle that sets off sparks, causing her to drop it on James's crotch. In his panic, he slips on some gel that Kate squeezed out earlier (and never cleaned up) and he falls ass-first onto a ballerina music box, which gets stuck up there. Maura tries to pull it out but cannot, and James leaves annoyed and in pain.

Brinda makes another attempt to get into the party, forcing Kate to confront her over why she hates Brinda. This leads to Brinda calling Kate a hothead, making her flip out and giving Brinda an opportunity to take a picture of her crazy self and put it on social media. Moments later, Kate gets a call from Haley, who is with her grandparents. She sees the picture of Kate at the party, still convinced that her mom hasn't changed. Haley calls her mom a loser. Upset, Kate ditches the party mom thing and starts to drink. When she goes out to get more booze, she grabs Maura's bag and looks at her phone to hear a message from Haley, learning that Haley has been staying not with a friend, but with Maura.

The sisters, realizing each other's deceptions, confront each other outside the house. Kate left the car running and didn't put the brakes on, so it pushes the sister tree over and it falls on the side of the house. Then a sinkhole swallows up the pool. The sisters fight in the mud, just as their parents arrive with Haley. Seeing the two of them like this, Haley is angry, but she slips into the sinkhole and falls into the pool. Kate jumps in after her, and everyone helps the two of them climb back out.

Kate and Maura are forced to own up to their mistakes by their parents. Kate admits she never got a job, but she is on slightly better terms with Haley. Bucky and Deanna force them to clean up the house. Over the next two weeks, the sisters try to do right and fix the house with the help of their friends. By the end of it, Brinda, having patched things up with Kate, helps sell the house again, to Alex and Hae-Woo, his new girlfriend. Brinda is now with Dave too, despite Kate telling her that he has chlamydia. The sisters reconcile, and Kate urges Maura to go after James. She goes to his house and lies facedown in the pool to call for help. James walks into the pool and kisses her.

4 months later, it's Christmas-time. The sisters, along with James and Haley, go to their parents' home to celebrate. Kate and Maura hug and then start to do a goofy dance.

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