BACKGROUND The relationship between coronary heart disease (CHD) and the paraoxonase 2 (PON2) Ser311Cys polymorphism has received much attention. We conducted a meta-analysis on the results from published case-control studies examining this relation. MATERIAL AND METHODS A literature search was performed using PubMed and ISI Web of Knowledge databases until October 2015. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using Stata version 11.0 software. Data were pooled using the random-effects model. RESULTS Nine studies were eligible for statistical analysis and included a total of 5278 participants. The results did not support an association between the Ser311Cys polymorphism and CHD in the overall populations (Asians, Caucasians, and a Hispanic mixed population) under dominant (OR 1.07; 95% CI 0.91-1.28; Pz=0.413), recessive (OR 1.19; 95% CI 0.72-1.95; Pz=0.500), homozygote (OR 1.20; 95% CI 0.71-2.03; Pz=0.489), and allelic comparison (OR 1.08; 95% CI 0.91-1.28; Pz=0.390) models. However, in subgroup analysis according to ethnicity, we found that the Ser311Cys polymorphism was associated with CHD risk in Caucasians under recessive (OR 2.08; 95% CI 1.30-3.34; Pz=0.002) and homozygote (OR 2.16; 95% CI 1.33-3.50; Pz=0.002) models. Subgroup analysis indicated no significant association of this polymorphism with CHD in either Asian or Hispanic populations. CONCLUSIONS The PON2 Ser311Cys polymorphism is associated with CHD risk in Caucasians, but there is no association between this polymorphism and CHD in Asians or Hispanic populations.