Mammalian cells are constantly exposed to a wide variety of genotoxic agents from both endogenous and exogenous sources. Genetic variability in DNA repair may contribute to human cancer risk. In this population-based case-control study in China, we tested the hypothesis that a C to T variant (Thr241Met) of DNA repair gene XRCC3 (X-ray repair cross-complementing group 3) is associated with risk of developing gastric cancer. We genotyped for this variant using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) in 188 histologically confirmed gastric cancer patients and 166 frequency-matched cancer-free controls. The XRCC3 genotype and allele frequencies were not significantly different between cases and controls (P = 0.99 for genotype; P = 0.76 for allele). The XRCC3 241Met allele frequency (4.8%) was significantly lower in healthy Chinese controls than previously reported healthy US Caucasian controls (38.9%). Compared with the XRCC3 241Thr/Thr genotype, the variant XRCC3241Thr/Met and Met/Met genotypes were not associated with an increased risk of gastric cancer (adjusted odds ratio (OR(a)), 1.06; 95% confidence interval (CI), 0.52-2.16). These findings suggest that polymorphisms of XRCC3 Thr241Met may not play a role in the etiology of gastric cancer. Further studies with a larger number of subjects and simultaneous measurement of different polymorphisms in DNA repair genes in the same pathway are needed to confirm these findings.