To investigate the association between endothelin-converting enzyme-1b (ECE-1b) C-338A polymorphism and gastric cancer risk, we conducted a hospital-based case-control study of 256 gastric cancer cases and 256 controls matched on age and gender. The genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism. We found that the genotype frequencies were significantly different (P=0.005) between cases and controls. Compared with the wild genotype CC, the variant genotypes (CA+AA) were associated with a 64% increased risk of gastric cancer [adjusted odds ratio (OR)=1.64, 95% confidence interval (CI) 1.15-2.33]. Further stratification analyses indicated that the increased risk was especially noteworthy in older subjects (age 58) (adjusted OR=1.91, 95% CI 1.18-3.09), women (adjusted OR=2.30, 95% CI 1.11-4.79) and non-smokers (adjusted OR=1.79, 95% CI 1.19-2.67). Our results suggest that the ECE-1b C-338A polymorphism may be associated with increased risk of gastric cancer.