New additions to the cast are comedian Jon Reep and former Daily Show correspondents Rob Corddry and Ed Helms. Other cast members include David Krumholtz, Eddie Kaye Thomas, Jack Conley, Roger Bart, Danneel Harris, Eric Winter, Adam Herschman, and Richard Christy.
The film was released on April 25, 2008 by Warner Bros.; this film was the first New Line Cinema title to be distributed by Warner Bros. since New Line Cinema became a division of Warner Bros. The film was released on DVD and Blu-Ray Disc on July 29, 2008.
Following the events of Harold & Kumar Go to White Castle, Harold Lee and Kumar Patel fly to Amsterdam so Harold can pursue a budding romance with his neighbor. The pair run into Vanessa, Kumar's ex-girlfriend, and her fiancee, Colton in the airport. Harold and Kumar board the plane, and mid-flight, an old woman sees Kumar lighting his new invention, a smokeless bong, screams "terrorist!". Air marshals immediately detain both, and the plane returns to Washington, where Ron Fox, a neurotic undersecretary of Homeland Security, sends them to the Guantanamo Bay detention camp. They escape, and decide to travel to Texas in search of Colton, with hopes that he will be able to help them through his father, who is connected with several high political officials.
The film follows the same path as its predecessor, putting Harold and Kumar in a series of quirky 'episodes', usually centered around themes of drugs, sex, and racism. Neil Patrick Harris returns as his drug-addled, womanizing parody of himself.
After being betrayed by Colton and jumping out of a plane, the pair falls through the ceiling of President George W. Bush's home in Texas, where the President is hiding from Dick Cheney. After bonding over marijuana, the President pardons the pair and sends the Secret Service to help them. Harold and Kumar arrive at the wedding just in time to stop it, revealing Colton's true nature. Enraged, Colton attacks Kumar, but Harold levels him. Vanessa is angry at Kumar for embarrassing her at the wedding, but forgives him when he recites the poem that he had been writing on the day they met, but was too embarrassed to share with her until now. The three leave the wedding, heading to Amsterdam, where Harold finds Maria. The movie ends with everyone enjoying the city and its offerings.
Not all reviews were so glowing; Richard Roeper of At the Movies lamented that although he enjoyed the "pot-fueled laughs and the sheer energetic lunacy of the original, I was really let down by this uninspired sequel. The New York Daily News said that "the movie forgets to stay true to their characters or to itself. Michael Phillips of The Chicago Tribune wrote that you "find yourself smiling at some of the bits, wincing through many, many others, and ultimately wondering if the pacing would've improved had either H or K developed a terrible cocaine habit. Amnesty International USA commented by saying that "Guantanamo is no joke." They have encouraged their membership to hand out fliers at movie theater screenings to promote awareness about the treatment of detainees at the Guantanamo Bay detention camp.
In its opening weekend, the film grossed $14.9 million in 2,510 theaters, in the United States and Canada, averaging $5,939 per theater and ranking #2 at the box office behind Baby Mama. Harold & Kumar Escape from Guantanamo Bay performed much better at the box office than Harold & Kumar Go to White Castle which grossed $23.9 million worldwide after opening at #7 in the United States and Canada with $5.4 million. As of July 18, the film grossed $40.43 million worldwide.