Celebrating his impending marriage to Tracy Garner, Doug Billings and his friends Phil Wenneck, Stuart "Stu" Price, and Tracy's brother Alan travel to Las Vegas for a bachelor party, staying at Caesars Palace.
The next morning, Phil, Stu and Alan awaken to find they have no memory of the previous night and Doug is nowhere to be found. Stu is missing a tooth, their hotel suite is in disarray, a tiger is in their bathroom, and a baby is in the closet. They find Doug's mattress impaled on a statue outside of their hotel and when they ask for their Mercedes, the valet delivers a police cruiser.
Following clues to their steps, the trio travel to a hospital where they discover they were drugged with rohypnol, causing their memory loss, and that they came to the hospital from a chapel. At the chapel they learn that Stu married a stripper, Jade, despite having a long-term relationship with his mean-spirited girlfriend. Outside the chapel, the trio are attacked by gangsters saying they are looking for someone. They flee and visit Jade, discovering that she is the mother of the baby, before being arrested by the police.
Having been told that the Mercedes has been impounded, the trio is released when they volunteer to be targets for a taser demonstration. While driving the Mercedes, they discover a naked man in the trunk who attacks them and flees. Alan confesses that he drugged their drinks to ensure they had a good night, thinking that they were ecstacy.
Returning to their villa, they find Mike Tyson, who orders the trio to return the tiger to his mansion immediately. Stu drugs the tiger with the remaining roofies and they drive towards Tyson's home in the Mercedes, but the tiger attacks them and damages the car's interior. After pushing the car the rest of the way to avoid the tiger, Tyson shows the trio footage of them stealing the tiger to help them locate Doug. While driving, their car is struck by another vehicle intentionally; the passengers are revealed to be the gangsters from the chapel and their boss, Leslie Chow – the naked man from their trunk – who accuses the trio of stealing $80,000 of his money and kidnapping him. Chow says he has their "friend", threatening to kill him if his money is not returned. Unaware of the location of Chow's $80,000, Alan, with help from Stu and Jade, uses his knowledge of card counting to win $82,400 playing Blackjack. They meet with Chow and exchange the money, only to find that "Doug" is the drug dealer who inadvertently sold Alan the roofies.
With the wedding occurring in hours, Phil tells Tracy they cannot find Doug. Following a conversation with "Black Doug", Stu realizes where Doug is. The trio travel back to their hotel where they find Doug on the roof, moved there on his mattress while he was asleep, as a practical joke by Stu, Phil and Alan. Before leaving, Stu makes arrangements to meet with Jade the following week to pursue a relationship. With less than four hours before the wedding and with no flights available, the foursome race home, with Doug revealing he has possession of Chow's original $80,000. Despite their late arrival, Doug and Tracy are married and Stu breaks up with his girlfriend. As the reception ends, Alan finds Stu's digital camera detailing the events they cannot remember and the four agree to look at the pictures together before deleting the evidence of their exploits.
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