Director Sylvain White was attracted by the realistic nature of the comic to do the film: "What appealed to me about The Losers was that it wasn't the typical superhero-with-superpowers thing. It was based on real characters-realistic characters - and based in reality, like a lot of the European graphic novels that I had grown up reading."
Originally Tim Story was to direct, citing influences from the war drama Black Hawk Down (2001) and the television miniseries Band of Brothers (2001): "I was looking for a film that would have edge, but I wanted to keep the tongue-and-cheek, where the characters have a little fun with each other." He was later replaced with Sylvain White.
When Wade notices Pooch flying the Miami Police helicopter, he is looking through his binoculars the correct way. In the second shot, his binoculars are backwards.
When Cougar is running across the shipment containers at the Port of Los Angeles to set up his sniper position, the neck of the cello case on his back with his sniper rifle is flopping around when he is running to leap and somersault from one container to the other, revealing that his long sniper rifle is not in it. He later pulls the rifle out already fully assembled so it can't be that it was disassembled inside the cello case.
In the shoot out scene at the end they are supposed to be in Los Angeles, but when they are on the docks and the crane you can clearly see in the background the coast of harbor of San Juan, Puerto Rico.