The film stars Luke Wilson, Vince Vaughn, and Will Ferrell as depressed men in their thirties who seek to relive their college days by starting a fraternity, and the tribulations they encounter in doing so.

Returning home early from a business trip, real estate attorney Mitch Martin walks in on his girlfriend Heidi hosting an orgy and breaks up with her.

At his friend Frank's wedding, Mitch makes an awkward impression on his high school crush, Nicole, and soon moves into a house near Harrison University campus in upstate New York.

A drunken Frank is seen streaking by his wife Marissa and her friends, straining their new marriage, while Mitch wakes up in bed with Darcie, a young woman he later learns is his boss' daughter and a high school senior.

Exploiting a university loophole, Bernard turns the house into a fraternity open to anyone, and the friends carry out hazing events throughout campus, much to Pritchard's displeasure.

Elderly World War II-veteran fraternity brother Blue dies of a heart attack during a "KY lube wrestling" match with two college girls at his birthday celebration, and Marissa asks Frank for a divorce.

Pritchard bribes student council president Megan Huang, promising to get her into Columbia Law School in exchange for revoking the fraternity's charter.

A badly burned Frank gives an intense rhythmic gymnastics performance, Bernard manages to complete the rings routine, and Weensie, an obese member chosen by Pritchard, executes a perfect vault landing.

The success of Road Trip prompted Armstrong and Phillips to pitch Reitman on a fraternity-themed film centered around adult men instead of the usual college-aged kids.

[7] Audiences surveyed by CinemaScore gave the film a grade B+ on a scale of A to F.[8] Elvis Mitchell of The New York Times called it a "sloppy, dumb, though occasionally funny comedy," comparing it to "a half-empty glass of Coke that's been sitting out for a couple of days; sure, it looks like cola, but one sip tells you exactly what's missing.

"[9] He called out both Phillips and co-executive producer Ivan Reitman for rehashing their previous works and accused the latter of self-plagiarism by saying that the film was "so derivative of Animal House (and, more specifically, its children) that it's like one of those by-the-numbers imitative movies Homer Simpson is so obsessed with.

"[9] Roger Ebert gave the film one out of four stars and stated, "This is not a funny movie, although it has a few good scenes and some nice work by Ferrell as an apparently compulsive nudist.

Also, The Dan Band sings one of the famous songs of Bonnie Tyler, "Total Eclipse of the Heart" (with some interesting improvisational departures as to the cover's lyrics), and Styx's "Lady".