While Blood Meridian initially received little recognition, it has since been recognized as McCarthy's masterpiece, and one of the greatest works of American literature.
Aleksandar Hemon has called Blood Meridian "possibly the greatest American novel of the past 25 years." In 2006, The New York Times conducted a poll of writers and critics regarding the most important works in American fiction from the previous 25 years; Blood Meridian was a runner-up, along with John Updike's four novels about Rabbit Angstrom and Don DeLillo's Underworld while Toni Morrison's Beloved topped the list. Novelist David Foster Wallace named Blood Meridian one of the five most underappreciated American novels since 1960 and described it as "[p]robably the most horrifying book of this century, at least [in] fiction."
Academics and critics have variously suggested that Blood Meridian is nihilistic or strongly moral; a satire of the western genre, a savage indictment of Manifest Destiny. Harold Bloom called it "the ultimate western;" J. Douglas Canfield described it as "a grotesque Bildungsroman in which we are denied access to the protagonist's consciousness almost entirely." Comparisons have been made to the work of Hieronymus Bosch and Sam Peckinpah, and of Dante Alighieri and Louis L'Amour. However, there is no consensus interpretation; James D. Lilley writes that the work "seems designed to elude interpretation." After reading Blood Meridian, Richard Selzer declared that McCarthy "is a genius--also probably somewhat insane." Critic Steven Shaviro wrote:
In the entire range of American literature, only Moby-Dick bears comparison to Blood Meridian. Both are epic in scope, cosmically resonant, obsessed with open space and with language, exploring vast uncharted distances with a fanatically patient minuteness. Both manifest a sublime visionary power that is matched only by still more ferocious irony. Both savagely explode the American dream of manifest destiny (sic) of racial domination and endless imperial expansion. But if anything, McCarthy writes with a yet more terrible clarity than does Melville.— Steven Shaviro, "A Reading of Blood Meridian"
American literary critic Harold Bloom praised Blood Meridian as one of the 20th century's finest novels. Time magazine included the novel in its "TIME 100 Best English-language Novels from 1923 to 2005".