Objectives: Genetics polymorphism of the E-selectin affects the pathogenesis of atherosclerosis and associated with coronary artery disease (CAD). We aimed to investigate the association between the rs5368 and rs3917406 polymorphisms in E-selectin genes and premature CAD (PCAD) in Chinese Han population. Methods: PCAD 628 patients and 732 controls were included in the study. E-selectin of rs5368 and rs3917406 polymorphisms were analyzed by polymerase chain reaction (PCR). Results: The frequencies of T allele of the rs5368 and rs3917406 polymorphisms were 27.2% and 47.8%, respectively, in the PCAD group, and 30.5% and 42.8% in the control group. The frequency of the T allele of the rs3917406 polymorphism was significantly higher in the PCAD group than in the control group (x(2) = 6.857, P = 0.009). In contrast, no statistically significant difference was found between controls and patients in the frequency of T allele of the rs5368 polymorphism. The univariate analysis showed that the E-selectin rs3917406 polymorphisms was associated with the PCAD in additive model (OR = 1.226, 95% CI = 1.05-1.43, P = 0.010) and dominant model (OR = 1.406, 95% CI = 1.11-1.78, P = 0.005). After adjusting for potential confounding variables the rs3917406 polymorphisms was independently associated with PCAD in additive model (OR = 1.347, 95% CI = 1.12-1.62, P = 0.002) and dominant model (OR = 1.669, 95% CI = 1.26-2.21, P < 0.001). The E-selectin rs5368 polymorphisms were not associated with PCAD in univariate and multivariate analyses of three models. Conclusion: Among the Chinese Han population, the rs3917406 polymorphism of the E-selectin gene was associated with PCAD in univariate and multivariate analysis, however, no significant correlation between the E-selectin rs5368 polymorphism and PCAD.