As Stu Price (Bradley Cooper) prepares for his wedding to Lauren, he makes a deliberate decision to steer clear of the mayhem that transpired two years ago in Las Vegas. At first, he turns down invitations from his closest companions—Doug Billings and Phil Wenneck (Ed Helms, Zach Galifianakis)—to join him on a trip to Thailand, favoring a subdued bachelor party at an IHOP instead. However, after some persuasion from Tracy, Stu finally agrees to bring along his friends, Tracy, and Phil's wife, Stephanie, embarking on a wild adventure complete with Lauren's 16-year-old brother, Teddy, a brilliant Stanford student. During the rehearsal dinner, a stern toast from Lauren's father hints at the trouble that lies ahead.
The next day, Stu, Phil, and Alan awaken in a rundown hotel room in Bangkok, completely unaware of how they ended up there or the night's debauchery. In the chaos, they discover that Stu now sports a tattoo that closely resembles one belonging to Mike Tyson, while Alan's head has been shaved. Their confusion escalates with the arrival of a chain-smoking monkey, who portends the havoc that will follow. To their dismay, they soon realize that Leslie Chow, a figure from their past, is in Thailand because of Alan’s previous invitation. In a crazed moment, they mistakenly think Chow has died and hastily stow his body in an ice box.
As they search for answers, a dubious clue from Doug—who left early—leads them to a police station in hopes of finding Teddy. Instead, they encounter a silent, wheelchair-bound Buddhist monk who offers no assistance. Their quest soon brings them to the charred remains of a club that met a fiery fate amidst the city’s anarchy. In their pursuit for clues, they visit the tattoo parlor where Stu got his ink, only to unearth a maze of tangled events spiraling out from that night of chaos. Returning the enigmatic monk to his temple opens up an opportunity for reflection, where Alan recalls their wild night at the strip club, unveiling a shocking detail about Stu's escapade with a transsexual woman.
Just as they think they’ve pieced things together, they find themselves confrontationally ambushed by ruthless Russian mobsters who abscond with the monkey and leave Phil wounded. In the aftermath of the fight, Alan admits to drugging marshmallows intended for Teddy, inadvertently mixing up the bags in a frenzy of poor planning. This leads to turmoil within the group as they grapple with the repercussions of their blunders. A vital clue appears when they discover an address inscribed on Alan's stomach, hinting at a meeting with Kingsley—a dangerous character who demands Chow's bank account password by morning in exchange for Teddy.
In a thrilling sequence of events, they are stunned to learn that Chow is, in fact, still alive and must engage in a frantic car chase against the Russian mobsters to rescue their missing friend. When they finally obtain the password, the trio completes their desperate transaction with Kingsley, only to be caught by Interpol agents who expose his true identity as an undercover operative. With tension mounting, they face a city-wide blackout that propels Stu to suddenly realize where Teddy is located.
Rushing back to their hotel, they feel a wave of relief upon discovering Teddy safe and sound in the elevator, though missing a finger after his ill-fated quest for ice. With Chow’s speedboat at their disposal, the group attempts to return to the wedding reception and shake off the chaos they recently endured. As they arrive, just in time to prevent Lauren's father from calling off the wedding, Stu delivers a heartfelt speech that expresses his unconventional side with such vigor that it impresses Lauren's father, ultimately bringing his approval to the union.
The wedding reception evolves into a vibrant celebration, especially when Alan presents Stu with an unexpected gift—a surprise musical performance by none other than Mike Tyson himself. As the night progresses, Teddy stumbles upon a treasure trove of photographic memories he captured, which he realizes he cannot delete due to a dead battery. The group, now joined by Tyson, revels in the recollections of their unforgettable escapades, deciding together what to do with the treasured photos that capture their night forever.
