Sam Lawton (Nicholas D'Agosto), is on his way to a company retreat with his coworkers. While crossing the North Bay Bridge, Sam suffers a premonition that the bridge will collapse, killing everyone and himself, except for his ex-girlfriend Molly Harper (Emma Bell). Panicked, he persuades Molly, his friends Peter Freidkin (Miles Fisher) and Nathan Sears (Arlen Escarpeta), Peter's girlfriend Candice Hooper (Ellen Wroe), his boss Dennis Lapman (David Koechner), Candice's rival Olivia Castle (Jacqueline MacInnes Wood) and coworker Isaac Palmer (P.J. Byrne) to leave the bridge before it collapses. Following the memorial service, local coroner William Bludworth (Tony Todd) mysteriously warns the survivors that they cheated Death. They ignore his warnings and move on with their lives.
Later, Candice goes to gymnastics practice with Peter, but a chain reaction causes her to fall off the highbars and snap her spine. The next day, Isaac is killed when his head is crushed by a falling Buddha statue during an acupuncture session at a Chinese spa. Bludworth, who has been present for both deaths so far, tells the remaining survivors that if they wish to cheat Death, they must kill someone who was never meant to die on the bridge, and thereby claim their remaining lifespan. Sam and Molly suspect that Olivia, who has gone for laser eye surgery, is next and that she's in danger. They arrive at the clinic but are too late to see her fall to her death from a window onto a car's windshield. Later, after Sam and Molly studied Death's design, they notice that Nathan is next on Death's list.
Meanwhile, Nathan, who has returned to the plant, accidentally kills his antagonistic co-worker Roy Carlson (Brent Stait) during an argument between the two when he shoves him in the path of a lifting hook, impaling his head. Nathan relays this information to the remaining survivors, who suggest that it means Nathan was successfully able to claim Roy's remaining lifespan and thus was skipped over. When Dennis arrives to question Nathan about the incident, he is suddenly killed when a stray wrench is launched by a belt sander, penetrating his head.
That evening, Sam's mentor allows him to become an apprentice in Paris. He allows Sam to have the restaurant to himself for a date with Molly. Peter, who has now been driven paranoid and insane by Candice's death, interrupts the date in order to inform them that he nearly pushed a stranger in front of a truck after convincing himself that he would be able to kill someone else in order to take their lifespan; subsequently, he has decided to kill Molly and take her remaining lifespan for himself. After Peter draws a gun and fires shots, Sam and Molly both escape to the restaurant's kitchen. Nearby outside, Agent Block (Courtney B. Vance) overhears the shots and enters the restaurant. He arrives during the confrontation, but is shot and killed by Peter. Believing he is now safe from Death for taking Block's lifespan, he decides to kill both Molly and Sam to remove any witnesses. After some struggling, Sam kills Peter with a meat spit before he can harm Molly.
Two weeks later, Sam and Molly are boarding a plane to Paris. As they are taking their seats, a fight breaks out between two passengers, revealed to be Carter Horton and Alex Browning, resulting in their removal from the plane with the other passengers. The plane that Sam and Molly are boarding is revealed to be Flight 180. In mid-air, the plane starts to break apart. Realizing they are too late to save themselves, both are killed in the resulting accident.
Meanwhile, at Roy's memorial, Nathan learns from a co-worker, John (Roman Podhora) that Roy's autopsy had revealed that Roy had a brain aneurysm that doctors said could have killed him in a matter of days. As Nathan realizes that he only saved himself for a short period of time, the landing gear from Flight 180 crashes through the roof of the building and crushes him setting off the events of the first four films.
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