Psychosocial factors have been reported to be independently associated with coronary heart disease. However, previous studies have been in mainly North American or European populations. The aim of the present analysis was to investigate the relation of psychosocial factors to risk of myocardial infarction in 24767 people from 52 countries. We used a case-control design with 11119 patients with a first myocardial infarction and 13648 age-matched (up to 5 years older or younger) and sex-matched controls from 262 centres in Asia, Europe, the Middle East, Africa, Australia, and North and South America. Data for demographic factors, education, income, and cardiovascular risk factors were obtained by standardised approaches. Psychosocial stress was assessed by four simple questions about stress at work and at home, financial stress, and major life events in the past year. Additional questions assessed locus of control and presence of depression. People with myocardial infarction (cases) reported higher prevalence of all four stress factors (p<0.0001). Of those cases still working, 23.0% (n=1249) experienced several periods of work stress compared with 17.9% (1324) of controls, and 10.0% (540) experienced permanent work stress during the previous year versus 5.0% (372) of controls. Odds ratios were 1.38 (99% CI 1.19-1.61) for several periods of work stress and 2.14 (1.73-2.64) for permanent stress at work, adjusted for age, sex, geographic region, and smoking. 11.6% (1288) of cases had several periods of stress at home compared with 8.6% (1179) of controls (odds ratio 1.52 [99% CI 1.34-1.72]), and 3.5% (384) of cases reported permanent stress at home versus 1.9% (253) of controls (2.12 [1.68-2.65]). General stress (work, home, or both) was associated with an odds ratio of 1.45 (99% CI 1.30-1.61) for several periods and 2.17 (1.84-2.55) for permanent stress. Severe financial stress was more typical in cases than controls (14.6% [1622] vs 12.2% [1659]; odds ratio 1.33 [99% CI 1.19-1.48]). Stressful life events in the past year were also more frequent in cases than controls (16.1% [1790] vs 13.0% [1771]; 1.48 [1.33-1.64]), as was depression (24.0% [2673] vs 17.6% [2404]; odds ratio 1.55 [1.42-1.69]). These differences were consistent across regions, in different ethnic groups, and in men and women. Presence of psychosocial stressors is associated with increased risk of acute myocardial infarction, suggesting that approaches aimed at modifying these factors should be developed.