Tobacco use is one of the major avoidable causes of cardiovascular diseases. We aimed to assess the risks associated with tobacco use (both smoking and non-smoking) and second hand tobacco smoke (SHS) worldwide. We did a standardised case-control study of acute myocardial infarction (AMI) with 27,089 participants in 52 countries (12,461 cases, 14,637 controls). We assessed relation between risk of AMI and current or former smoking, type of tobacco, amount smoked, effect of smokeless tobacco, and exposure to SHS. We controlled for confounders such as differences in lifestyles between smokers and non-smokers. Current smoking was associated with a greater risk of non-fatal AMI (odds ratio [OR] 2.95, 95% CI 2.77-3.14, p<0.0001) compared with never smoking; risk increased by 5.6% for every additional cigarette smoked. The OR associated with former smoking fell to 1.87 (95% CI 1.55-2.24) within 3 years of quitting. A residual excess risk remained 20 or more years after quitting (1.22, 1.09-1.37). Exclusion of individuals exposed to SHS in the never smoker reference group raised the risk in former smokers by about 10%. Smoking beedies alone (indigenous to South Asia) was associated with increased risk (2.89, 2.11-3.96) similar to that associated with cigarette smoking. Chewing tobacco alone was associated with OR 2.23 (1.41-3.52), and smokers who also chewed tobacco had the highest increase in risk (4.09, 2.98-5.61). SHS was associated with a graded increase in risk related to exposure; OR was 1.24 (1.17-1.32) in individuals who were least exposed (1-7 h per week) and 1.62 (1.45-1.81) in people who were most exposed (>21 h per week). Young male current smokers had the highest population attributable risk (58.3%; 95% CI 55.0-61.6) and older women the lowest (6.2%, 4.1-9.2). Population attributable risk for exposure to SHS for more than 1 h per week in never smokers was 15.4% (12.1-19.3). Tobacco use is one of the most important causes of AMI globally, especially in men. All forms of tobacco use, including different types of smoking and chewing tobacco and inhalation of SHS, should be discouraged to prevent cardiovascular diseases.