Endothelial nitric oxide synthase (eNOS) -786T→C and 894G→T polymorphisms have been associated with eNOS dysfunction, which might further compromise microcirculatory blood flow during sepsis and increase the risk of organ injury. The purpose of this study is to investigate the association of those two eNOS gene polymorphisms with the severity of organ dysfunction and outcome in patients with severe sepsis.A cohort of patients with severe sepsis was studied and genotyped for eNOS -786T→C and 894G→T polymorphisms. Acute Physical and Chronic Health Evaluation score, the Sequential Organ Failure Assessment score, with or without shock, and the outcomes were compared in patients with different genotypes.One hundred seventeen patients fulfilled with inclusion criteria were enrolled from nine intensive care units of academic hospital in Beijing. In comparison with the GG genotype, patients with the GT genotype (894G→T) had a trend toward an increase in the frequency of shock (87% vs. 68.1%, p=0.071) and significantly fewer days to shock onset (p<0.05). Those patients also had significantly higher Acute Physical and Chronic Health Evaluation II scores (p<0.05), Sequential Organ Failure Assessment scores (p<0.001), and mortality at both 7 days and 28 days (p<0.001). Multivariate analyses identified the GT genotype (894G→T) as an independent risk factor for outcome in patients with severe sepsis. However, we found that the eNOS -786T→C polymorphism was not associated with severity of disease or mortality of patients with sepsis.Carriage of the GT genotype at 894 of eNOS gene was associated with the occurrence of shock and impaired organ function.