Doug Billings, a cheerful and careful bachelor, travels to Las Vegas with his best friends Phil Wenneck, a sarcastic Elementary School teacher, and Stu Price, an apprehensive dentist. He also brings Alan Garner, his future brother-in-law who is immature and eccentric. Sid, the father of his fiancée Tracy, allows Doug to drive his vintage Mercedes-Benz W111 to Vegas from Los Angeles. They get a suite in Caesars Palace, and celebrate by sneaking onto the hotel rooftop and taking shots of Jägermeister. The next morning, Phil, Stu, and Alan awaken to find they have no memory of the previous night; Doug is nowhere to be found, Stu’s tooth is missing, the suite is a disaster, a Bengal tiger is in the bathroom, and a baby is in the closet. They see Doug’s mattress impaled on a statue outside and when they ask for their Mercedes, the valet delivers an LVPD police cruiser.
Retracing their steps, the trio travel to a hospital where they discover they were drugged with Rohypnol (roofies), causing their memory loss, and that they went to the hospital from a chapel the previous night. At the chapel, they learn that Stu married an escort named Jade, despite being in a long-term relationship with his domineering and philandering girlfriend Melissa. Outside the chapel, the trio is attacked by gangsters saying they are looking for someone. They flee and track down Jade, the mother of the baby.
They are then arrested by the police for having stolen the police cruiser. After being told that the Mercedes was impounded, the trio are released when they unwittingly volunteer to be targets for a taser demonstration. While driving the Mercedes, they discover a naked Chinese man named Mr. Chow in the trunk, who beats the trio with a crowbar and flees. Alan confesses that he drugged their drinks to ensure they had a good night, believing the drug to be ecstasy.