Little is known about the relationship between gut dysbiosis, inflammation, and adverse outcomes in patients with chronic kidney disease. We examined the association of microbial diversity with all-cause mortality in hemodialysis patients. The gut microbiota was assessed by 16S ribosomal RNA gene sequencing. During a median follow-up of 2.1 years, the adjusted risk of death among patients with higher diversity (above median) was 74% lower than that among patients with lower diversity (below median). We then compared the microbial composition between nonsurvivors and survivors in a matched case-control study. We observed significantly lower microbial diversity and higher proinflammatory cytokines among nonsurvivors than survivors. Specifically, the relative abundance of Succinivibrio and Anaerostipes, two short-chain fatty acid-producing bacteria, was markedly reduced in nonsurvivors. Thus, a unique gut microbial composition is associated with an increased risk of mortality among hemodialysis patients and may be used to identify subjects with a poor prognosis.