The XRCC3 gene has been suggested to play an important role in the pathogenesis of leukemia risk. But the findings of publications are contradictory. To derive a more precise estimation of the association, we performed a meta-analysis. The PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases were searched for case-control studies published up to August 2013. The pooled odds ratio (OR) and its corresponding 95% confidence interval (CI) were calculated by using a fixed- or random-effect model. A total of 15 case-control studies met the inclusion criteria and were selected. The pooled OR showed that there was no statistically significant association between XRCC3 Thr241Met polymorphism and leukemia risk in overall including studies, while a risky association was observed for acute myeloid leukemia (AML) (dominant model TT/TC vs. CC: OR = 1.240, 95% CI = 1.018-1.511, P = 0.032). The XRCC3 Thr241Met polymorphism might be associated with risk of leukemia in AML. More studies with larger sample sizes are needed to validate this result.