MDM2 is a phosphoprotein that interacts with p53 and inhibits its activity. Recently, a T to G substitution (SNP309) in the promoter of MDM2 was identified and associated with increased MDM2 expression and a significantly earlier age of onset of several tumors, including colorectal cancer. Several studies evaluated the association between SNP309 and colorectal cancer risk in diverse populations. However, the results remain conflicting rather than conclusive. To derive a more precise estimation of association between MDM2 SNP309 and risk of colorectal cancer, we performed a meta-analysis of 3347 colorectal cancer cases and 3102 controls from eight published case-control studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. The results suggested that the variant genotype was associated with a significantly increased colorectal cancer risk (GT vs. TT: OR=1.19, 95% CI=1.06-1.35; p=0.005). In the stratified analyses, significantly increased risks were found among Asian populations (OR=1.28, 95% CI=1.10-1.50; p=0.002) and population-based studies (OR=1.18, 95% CI=1.03-1.34; p=0.016). Although some bias could not be eliminated, this meta-analysis suggested that the MDM2 SNP309 polymorphism is a low-penetrance risk factor for the development of colorectal cancer, particularly among Asians.