The C3435T (Ile1142Ile) polymorphism of the multidrug resistance gene (MDR1) has been implicated in leukemia risk, but the reported results are inconsistent. Here we performed a meta-analysis to evaluate the association between C3435T polymorphism and the risk of leukemia using all case-control studies published before June 2011 according to PubMed. A total of 10 case-control studies were included in this analysis. We found that variant genotypes of C3435T (CT/TT) were significantly associated with an increased risk of leukemia (CT/TT vs. CC: odds ratio [OR] = 1.29; 95% confidence interval [CI] = 1.11-1.50, p = 0.284 for heterogeneity test). Additionally, the association was more significant in chronic leukemia (specifically B-cell chronic lymphocytic leukemia [B-CLL]) (OR = 1.94; 95% CI = 1.32-2.85, p = 0.648 for heterogeneity test) than in acute leukemia (OR = 1.19; 95% CI = 1.01-1.40, p = 0.616 for heterogeneity test), p = 0.021 for heterogeneity test between groups. These findings provide further evidence that the MDR1 C3435T variant may modify the susceptibility to leukemia.