Objective Apolipoprotein A5 (APOA5) is associated with plasma triglyceride (TG) levels, a risk factor for coronary heart disease (CHD). This study explored the association between CHD and the APOA5 rs662799 polymorphism. Methods We collected 1,521 samples (783 CHD patients and 738 controls) for this case-control study. Meta-analysis was performed using Review Manager Software and Stata Software. Results Significant differences were observed between CHD cases and controls at the level of both genotype (chi(2) = 8.964, df = 2, P = 0.011) and allele (chi(2) = 9.180, df = 1, P = 0.002, OR = 1.275, 95% CI = 1.089-1.492). A breakdown analysis by gender showed a significant association of APOA5 rs662799 with CHD in males (chi(2) = 7.770, df = 1, P = 0.005; OR = 1.331, 95% CI = 1.088-1.628). An additional meta-analysis using 21378 cases and 28428 controls established that rs662799 is significantly associated with CHD (P < 0.00001). Conclusion Both our case-control study and meta-analysis confirm a significant association between APOA5 rs662799 and CHD. In addition, our results suggest a male-specific association between the APOA5 rs662799 polymorphism and CHD.