Human paraoxonase 1 (PON1) is a calcium-dependent high-density lipoprotein associated ester hydrolase that has attracted considerable attention as a candidate factor for coronary heart disease (CHD) based on its function as a key factor in lipoprotein catabolism pathways. This meta-analysis aimed to clarify the inconsistency of published studies and to establish a comprehensive picture of the relationship between PON1 activity and CHD susceptibility. A systematic search was performed from PubMed, Web of Science, EMBASE, and CNKI databases. Ratio of means (RoM) between case and control and 95% confidence intervals (CIs) were calculated using a random-effects model. The source of heterogeneity was explored by subgroup analysis and meta-regression. We identified 47 eligible studies including a total of 9853 CHD cases and 11,408 controls. The pooled analysis showed that CHD patients had a 19% lower PON1 activity than did the controls (RoM=0.81; 95% CI: 0.74-0.89, p<10(-5)). In the subgroup analyses by CHD end points, a similar effect size was observed with coronary stenosis and myocardial infarction subgroups, with corresponding RoM of 0.81 (95% CI: 0.73-0.89, p<10(-4)) and 0.83 (95% CI: 0.74-0.93, p=0.001), respectively. Decreased PON1 activity associated with CHD risk was observed in almost all subgroup analysis according to ethnicity, sample size, study design, mean age of cases, source, and type of control. Decreased PON1 activity may act as a risk factor for the development of CHD. Progressive decrease in serum PON1 activity may exist for an individual with severe disease. However, larger studies using a prospective approach are needed to confirm our results.