The relationship between murine double minute 2 (MDM2) T309G polymorphism and esophageal cancer risk has been discussed with discrepant results. The aim of our study is to investigate the systematic association between the potentially functional MDM2 T309G polymorphism and esophageal cancer risk. Eligible studies were included through searching the databases of PubMed, EMBASE, and Chinese National Knowledge Infrastructure (up to April 2014). The crude odds ratio (OR) and 95% confidence interval (CI) were used to estimate the strength of the association. Six published case-control studies, including 1899 cases and 3016 controls, were identified. Overall, our study suggested that MDM2 T309G polymorphism was significantly associated with increased risk of esophageal cancer (TT vs. GG: OR = 0.77, 95% CI = 0.65-0.90, P = 0.002; T vs. G: OR = 0.88, 95% CI = 0.81-0.96, P = 0.002). In subgroup analyses stratified by source of controls, ethnicity, and quality score assessment, respectively, similar results were obtained (TT vs. GG: OR = 0.65, 95% CI = 0.48-0.89, P = 0.007 for hospital-based studies; T vs. G: OR = 0.90, 95% CI = 0.81-0.99, P = 0.04 for population-based studies; and T vs. G: OR = 0.85, 95% CI = 0.78-0.93, P = 0.004 for Asians). The results of Begg's test and Egger's test did not suggest publication bias in the studies. Therefore, the MDM2 T309G polymorphism may be significantly associated with increased esophageal cancer risk, especially among Asians.