Contrary to a cardioprotective effect of moderate regular alcohol consumption, accumulating evidence points to a detrimental effect of irregular heavy drinking occasions (>60 g of pure alcohol or ≥5 drinks per occasion at least monthly) on ischemic heart disease risk, even for drinkers whose average consumption is moderate. The authors systematically searched electronic databases from 1980 to 2009 for case-control or cohort studies examining the association of irregular heavy drinking occasions with ischemic heart disease risk. Studies were included if they reported either a relative risk estimate for intoxication or frequency of ≥5 drinks stratified by or adjusted for total average alcohol consumption. The search identified 14 studies (including 31 risk estimates) containing 4,718 ischemic heart disease events (morbidity and mortality). Using a standardized protocol, the authors extracted relative risk estimates and their variance, in addition to study characteristics. In a random-effects model, the pooled relative risk of irregular heavy drinking occasions compared with regular moderate drinking was 1.45 (95% confidence interval: 1.24, 1.70), with significant between-study heterogeneity (I² = 53.9%). Results were robust in several sensitivity analyses. The authors concluded that the cardioprotective effect of moderate alcohol consumption disappears when, on average, light to moderate drinking is mixed with irregular heavy drinking occasions.