In 2009, he starred alongside Jake Gyllenhaal and Natalie Portman in the Jim Sheridan-directed war drama Brothers as Sam Cahill, a prisoner of war who returns from Afghanistan and starts believing that his wife has become romantically involved with his brother. He received critical acclaim and a Golden Globe nomination for his performance in the film. Of the nomination, Maguire said, "I had no expectation about getting a nomination, but I was watching nonetheless. My wife and my son got really excited. I was sort of surprised – I was like, 'Oh, wow.' And I couldn't hear the latter part of my name." Maguire lost to Jeff Bridges for his role in Crazy Heart. Gyllenhaal himself said that Maguire's acting in Brothers had influenced him. Maguire was also initially set to star as The Writer in Life of Pi (2012), directed by Ang Lee but was cut from the film during production for being "too recogniseable" and was replaced by Rafe Spall, with Lee deciding to reshoot the scenes he had shot with Maguire.
