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The movie opened with an estimated $77.4 million in America, breaking the previous record of $72.6 million set by The Lord of the Rings: The Return of the King in December 2003.
The film made $59.2 million on Friday and Saturday, plus an additional $18.2 million on Sunday, although Warner Bros predicted that the latter figures could be an under-estimation.
I Am Legend is an adaptation of Richard Matheson's classic science-fiction novel of the same name. It tells the story of the lone human survivor in a post-apocalyptic USA, where the population has been turned into a form of vampires by a rogue virus.
Smith recently made a public apology for causing chaos in Manhattan while shooting the movie, after residents complained when Brooklyn Bridge and a number of streets in the city were closed.
The film is the studio's biggest ever success with a "non-franchise" feature.
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