•Bradley Cooper as Phil Wenneck, the groom's best friend, a school teacher who is bored with married life.
•Ed Helms as Dr. Stuart "Stu" Price, a dentist stuck in a bad relationship, friend of the groom.
•Zach Galifianakis as Alan Garner, the socially awkward, soon to be brother-in-law of the groom.
•Justin Bartha as Doug Billings, the soon-to-be groom who is taken to Las Vegas by his three best friends only to be lost after being drugged.
•Heather Graham as Jade, a kindly stripper/escort and single mother.
•Sasha Barrese as Tracy Garner, the bride.
•Rachael Harris as Melissa, Stu's hateful girlfriend. Harris previously co-starred with Helms on The Daily Show.
•Jeffrey Tambor as Sid Garner, father of the bride.
•Bryan Callen as Eddie Palermo, owner of the "Best Little Wedding Chapel".
•Rob Riggle as Officer Franklin, a police officer who arrests the guys for stealing a police car.
•Cleo King as Officer Garden, Franklin's partner.
•Matt Walsh as Dr. Valsh, a Las Vegas doctor.
•Ken Jeong as Leslie Chow a Las Vegas gangster who demands his lost prize money and apparently kidnaps Doug.
•Mike Epps as "Black Doug", a drug dealer mistaken for Doug Billings.
•Jernard Burks as Leonard, Mike Tyson's right-hand man.
•Ian Anthony Dale as Chow's #1
•Michael Li as Chow's #2
•Gillian Vigman as Stephanie Wenneck, Phil's wife.
•Sondra Currie as Linda Garner, mother of the bride.
•Nathalie Fay as Lisa, the hotel stewardess at Caesars Palace.
•Unknown as Tyler, Jade's baby son, who the guys call Carlos
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