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Abstract Background Numerous studies have investigated the relationship between COX-2 8473 T > C polymorphism and cancer susceptibility, however, the results remain controversial. Therefore, we carried out the present meta-analysis to obtain a more accurate assessment of this potential association. Methods In this meta-analysis, 79 case-control studies were included with a total of 38,634 cases and 55,206 controls. We searched all relevant articles published in PubMed, EMBASE, OVID, Web of Science, CNKI and Wanfang Data, till September 29, 2017. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the association. We performed subgroup analysis according to ethnicity, source of controls, genotyping method and cancer type. Moreover, Trial sequential analysis (TSA) was implemented to decrease the risk of type I error and estimate whether the current evidence of the results was sufficient and conclusive. Results Overall, our results indicated that 8473 T > C polymorphism was not associated with cancer susceptibility. However, stratified analysis showed that the polymorphism was associated with a statistically significant decreased risk for nasopharyngeal cancer and bladder cancer, but an increased risk for esophageal cancer and skin cancer. Interestingly, TSA demonstrated that the evidence of the result was sufficient in this study. Conclusion No significant association between COX-2 8473 T > C polymorphism and cancer risk was detected.