INTRODUCTION: To investigate the relationships between lipase gene polymorphisms and coronary artery disease (CAD) risk. EVIDENCE ACQUISITION: We searched PubMed, Embase and ISI web of science databases for articles estimated the association of S447X polymorphism with CAD. EVIDENCE SYNTESIS: Twelve-five articles were included in the meta-analysis. We found the G allele S447X polymorphism could reduce CAD risk by approximately 22% (OR=0.78. 95% CI: 0.71-0.84; fixed effects, I2=35.3%, P=0.07). Compared with non-carriers, individuals with two copies of the G allele had approximately 52% risks of CAD (OR=0.48, 95% CI: 0.29-0.68), and the individuals with GO and GC+GG had approximately 19% and 26% risks of CAD compared with those with CC genotype, respectively (GC versus CC: OR=0.81, 95% CI: 0.74-0.88; [GC+GG] versus CC: OR=0.74, 95% CI: 0.68-0.80). The G allelic significantly decreased risk of myocardial infarction (MI) (OR=0.74, 95% CI: 0.57-0.92). We found significant relationship between the variant and AMD in all the genetic models (GG versus CC: OR=0.48, 95% CI: 0.18-0.79; GC versus CC: OR=0.76, 95% CI: 0.57-0.94; [GG+GC] versus CC: OR=0.73, 95% CI: 0.64-0.83). CONCLUSIONS: The results indicated G allelic could significantly decrease CAD and MI risk.