Abstract: Summary Background Although more than 80% of the global burden of cardiovascular disease occurs in low-income and middle-income countries, knowledge of the importance of risk factors is largely derived from developed countries. Therefore, the effect of such factors on risk of coronary heart disease in most regions of the world is unknown. Methods We established a standardised case-control study of acute myocardial infarction in 52 countries, representing every inhabited continent. 15 152 cases and 14 820 controls were enrolled. The relation of smoking, history of hypertension or diabetes, waist/hip ratio, dietary patterns, physical activity, consumption of alcohol, blood apolipoproteins (Apo), and psychosocial factors to myocardial infarction are reported here. Odds ratios and their 99% CIs for the association of risk factors to myocardial infarction and their population attributable risks (PAR) were calculated. Findings Smoking (odds ratio 2·87 for current vs never, PAR 35·7% for current and former vs never), raised ApoB/ApoA1 ratio (3·25 for top vs lowest quintile, PAR 49·2% for top four quintiles vs lowest quintile), history of hypertension (1·91, PAR 17·9%), diabetes (2·37, PAR 9·9%), abdominal obesity (1·12 for top vs lowest tertile and 1·62 for middle vs lowest tertile, PAR 20·1% for top two tertiles vs lowest tertile), psychosocial factors (2·67, PAR 32·5%), daily consumption of fruits and vegetables (0·70, PAR 13·7% for lack of daily consumption), regular alcohol consumption (0·91, PAR 6·7%), and regular physical activity (0·86, PAR 12·2%), were all significantly related to acute myocardial infarction (p<0·0001 for all risk factors and p=0·03 for alcohol). These associations were noted in men and women, old and young, and in all regions of the world. Collectively, these nine risk factors accounted for 90% of the PAR in men and 94% in women. Interpretation Abnormal lipids, smoking, hypertension, diabetes, abdominal obesity, psychosocial factors, consumption of fruits, vegetables, and alcohol, and regular physical activity account for most of the risk of myocardial infarction worldwide in both sexes and at all ages in all regions. This finding suggests that approaches to prevention can be based on similar principles worldwide and have the potential to prevent most premature cases of myocardial infarction.