Gaylord "Greg" Focker is a nurse living in Chicago. He intends to propose to his girlfriend, Pam Byrnes, but his plan is disrupted when they are invited to the wedding of Pam's sister, Debbie, at their parents' house on Long Island. Greg decides to impress Pam's parents first, and propose to her in front of her family, but this plan is put on hold when the airline loses his luggage which contains the engagement ring.
At the Byrnes' house, Greg meets Pam's father, Jack; her mother, Dina; and Jack's beloved cat, Jinx. Jack becomes immediately suspicious towards Greg and openly criticizes him for his choice of career as a male nurse and anything else he sees as a difference between Greg and the Byrnes family. Greg attempts to impress Jack but his efforts fail. He becomes even more uncomfortable after he receives an impromptu lie detector test from Jack and later learns from Pam that Jack is a retired CIA operative.
Even after meeting the rest of Pam's family, Greg still feels like an outsider. Despite efforts to impress her family, his inadvertent actions make him an easy target for ridicule and anger. He unintentionally gives Debbie a broken nose and black eye during a pool volleyball game, uses a malfunctioning toilet which floods the Byrnes' backyard with sewage, and sets the wedding altar on fire. Several misunderstandings also cause Jack to believe Greg is a marijuana user after Pam's weed-using brother Denny frames him to avoid the wrath of his father. Jack also attempts to convince Pam that Greg was lying about taking the Medical College Admission Test due to being unable to find records of anyone named "Greg Focker" ever taking the test which Greg claimed he had passed with the initial intention of becoming a doctor. Later, Greg loses Jinx and replaces him with a stray whose tail he spray paints to make him look like Jinx in order to earn Jack's trust and approval, which succeeds. While out to dinner however, Jack receives a call from his neighbor that he has found the real Jinx and realizing Greg's deception tries to race home to expose him. Greg tries to beat him back but fails and it is discovered the duplicate cat has made a mess in the house and destroyed items for the wedding, including Debbie's dress.
By now, the entire Byrnes family, including Pam, have agreed that it is best for Greg to leave Long Island until the wedding concludes. Pam is upset at him for his lies about his previous misdeeds and begins to believe that Greg did indeed lie to her about the MCATs. Desperate to save himself, Greg reveals he has seen Jack engaging in some secret activity with some shady characters, and is planning a secret mission after the wedding and is still working for the CIA despite his claims of retirement. Jack angrily reveals that the secret mission was a surprise honeymoon for Debbie and her fiancé, and Greg realizes he only dug himself deeper into a hole. While leaving for the airport Greg's lost bag finally arrives and it is revealed his legal name is actually Gaylord Focker.
Unwillingly, Greg goes to the airport where he is detained by airport security for insisting that his luggage stays with him rather than be checked. After Pam contacts Greg's parents and receives his MCAT results (for which he aced) she confronts Jack and calls him out for being a jerk. After being told off by Dina over his consistent picking apart of any man Pam brings home (and that he didn't even like Pam's previous fiancée, Kevin, until after they broke up), and hearing Pam make a heartfelt call to Greg, Jack realizes that Pam truly loves Greg. Jack rushes to the airport, convinces airport security to release Greg and brings Greg back to the Byrnes' house after the two mend fences and after Greg promises Jack that he will be a loving, supportive husband to Pam.
As Greg is proposing to Pam, Jack and Dina listen in on their conversation from another room, agreeing that they should now meet Greg's parents (though both are visibly worried about this). After Debbie's wedding, Jack views footage of Greg recorded by hidden cameras that he had placed strategically around the house in which Greg calls Jack a "psycho" and mocks him and exposes Denny as the true marijuana user.
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