There have been a number of attempts to create a motion picture adaptation of Blood Meridian. However, all have failed during the development or pre-production stages. A common perception is that the story is "unfilmable", due to its unrelenting violence and dark tone. In an interview with Cormac McCarthy by The Wall Street Journal in 2009, McCarthy denied this notion, with his perspective being that it would be "very difficult to do and would require someone with a bountiful imagination and a lot of balls. But the payoff could be extraordinary."
Screenwriter Steve Tesich first adapted Blood Meridian into a screenplay in 1995. In the late 1990s, Tommy Lee Jones acquired the film adaptation rights to the story and subsequently rewrote Tesich's screenplay, with the idea of directing and playing a role in it. Due to film studios avoiding the project's overall violence, production could not move forward. 
Following the end of production for Kingdom of Heaven in 2004, screenwriter William Monahan and director Ridley Scott entered discussions with producer Scott Rudin for adapting Blood Meridian with Paramount Pictures financing. In an interview with Eclipse Magazine published in June 2008, Scott confirmed that the screenplay had been written, but that the extensive violence was proving to be a challenge for film standards. This later led to Scott and Monhan leaving the project, resulting in another abandoned adaptation.
By early 2011, James Franco was thinking of adapting Blood Meridian, along with a number of other William Faulkner and Cormac McCarthy novels. After being persuaded by Andrew Dominik to adapt the novel, Franco shot twenty-five minutes of test footage, starring Scott Glenn, Mark Pellegrino, Luke Perry and Dave Franco. For undisclosed reasons, Rudin denied further production of the film. On May 5, 2016, Variety revealed that Franco was negotiating with Rudin to write and direct an adaptation to be brought to the Marché du Film, with Russell Crowe, Tye Sheridan and Vincent D'Onofrio starring. However, later that day, it was reported that the project dissolved, due to issues concerning the film rights.
Lynne Ramsay has expressed an interest in adapting the novel.