Previous studies focusing on the association of PTGS2 polymorphism -765G>C with coronary artery disease (CAD) have failed to reach the same conclusion. In the present study, we performed a meta-analysis to systematically summarize the possible association between PTGS2 polymorphism -765G>C and the risk of CAD. We conducted a search of case-control studies on the associations of PTGS2 with susceptibility to CAD in PubMed, EMBASE, and Chinese National Knowledge Infrastructure databases. Data from eligible studies were extracted for meta-analysis. CAD risk associated with PTGS2 -765G>C was estimated by pooled odds ratios (ORs) and 95% confidence intervals (95%CI) with the RevMan 5.2 software. Eleven independent case-control studies on PTGS2 -765G>C were included in our meta-analysis. Our results showed that PTGS2 -765G>C was associated with a decreased risk of CAD (OR = 0.66, 95%CI = 0.56-0.79; P < 0.001). This meta-analysis suggests that PTGS2 -765G>C is associated with a decreased risk of CAD.