BACKGROUND: Although moderate alcohol use is associated with protection against myocardial infarction (MI), it is not known whether this effect is generalizable to populations worldwide. It is also uncertain whether differences in the pattern of alcohol use (and in particular heavy episodic consumption) between different regions negate any beneficial effect. METHODS AND RESULTS: We included 12 195 cases of first MI and 15 583 age- and sex-matched controls from 52 countries. Current alcohol use was associated with a reduced risk of MI (compared with nonusers: adjusted odds ratio, 0.87; 95% confidence interval, 0.80-0.94; P=0.001); however, the strength of this association was not uniform across different regions (region-alcohol interaction P<0.001). Heavy episodic drinking (≥6 drinks) within the preceding 24 hours was associated with an increased risk of MI (odds ratio, 1.4; 95% confidence interval, 1.1-1.9; P=0.01). This risk was particularly elevated in older individuals (for age >65 years: odds ratio, 5.3; 95% confidence interval, 1.6-18; P=0.008). CONCLUSIONS: In most participants, low levels of alcohol use are associated with a moderate reduction in the risk of MI; however, the strength of this association may not be uniform across different countries. An episode of heavy drinking is associated with an increased risk of acute MI in the subsequent 24 hours, particularly in older individuals.