Abstract Background Findings on the association between fish consumption and acute coronary syndrome are inconsistent. We assessed the role of fish consumption in acute coronary syndrome by conducting a dose-response meta-analysis. Methods We conducted a literature search of MEDLINE and Embase databases from 1966 to June 2013 for prospective cohort and case-control studies that evaluated the association between fish consumption and acute coronary syndrome among general populations without cardiovascular disease history. Additional studies were identified via hand search of references of relevant articles. Estimates of relative risk (RR) were pooled using random-effects model. Sex and age effects were also evaluated. Results Our search retrieved 11 prospective cohort and 8 case-control studies, totaling 408,305 participants. Among prospective cohort studies, the highest category of fish consumption (ie, ≥4 times per week) was associated with the greatest risk reduction in acute coronary syndrome (RR 0.79; 95% confidence interval CI, 0.70-0.89). In dose-response analysis, each additional 100-g serving of fish per week was associated with a 5% reduced risk (RR per serving 0.95; 95% CI, 0.92-0.97). Subgroup analysis and meta-regression suggested that the risk reduction did not differ across sex or age groups. No heterogeneity was observed among prospective cohort ( P  = .73) and case-control ( P  = .29) studies. There was no evidence of publication bias. Conclusion Our meta-analysis demonstrated that there is an inverse association between fish consumption and the risk of acute coronary syndrome. Fish consumption appears beneficial in the primary prevention of acute coronary syndrome, and higher consumption is associated with greater protection.