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Background and Objectives: Mortality from cardiovascular disease in the Middle East (ME) is projected to increase substantially by 2020. There are no large studies on the impact of risk factors for acute myocardial infarction (AMI) in the region. This is a report on the association of nine risk factors with AMI in the ME., Methods and Results: As part of the INTERHEART (IH) study, we enrolled 1364 cases of first AMI and 1525 matching controls from eight ME countries. The age at first AMI was 51.2 ± 10.3 years, which is the youngest, and with the largest proportion of patients <40 years in the entire IH population. The overall population attributable risk (PAR) of the nine risk factors to AMI was higher in the ME (97.5%) than worldwide (90.4%). Elevated apolipoprotein (Apo)B/ApoA1 had the strongest association with AMI, with odds ratio (OR) of 3.43 and PAR of 57.1%, followed by smoking (OR 3.63 and PAR 45.6%). ApoB/ApoA1 had greater association than the conventional low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol ratio. Both diabetes (OR 3.42, PAR 16.4%) and hypertension (OR 1.89, PAR 10.7%) had greater association with AMI in women than men. Abdominal obesity (OR 2.12, PAR 26.1%) and depression (OR 1.97, PAR 45.3%), but not conventional BMI, were significantly associated with AMI (p < 0.0001)., Conclusion: This is the largest prospective population study of risk factors associated with AMI in the ME. AMI occurs at younger age in the ME than all other regions. The PAR for the nine risk factors was higher in the ME (97.5%) than the rest of the world. These findings should guide serious prevention strategies.