Unveiled exclusively by Digital Spy, the footage features Miles Teller and Skylar Astin as Casey and Miller, two college students who decide to take their high school friend Jeff (Justin Chon) out for his 21st birthday.
Jeff is initially reluctant since his birthday falls on the eve of an important medical school interview, but Miller persuades him to come along for "just one drink", after which point the evening rapidly descends into mayhem.
Sarah Wright also features in the clip as love interest Nicole, while the film's supporting cast includes Francois Chau and Jonathan Keltz.
The Hangover co-writers Jon Lucas and Scott Moore reunited to pen 21 & Over, which also marks their directorial debut.
21 & Over is released in the UK on May 3.