Objective: We conducted this study to determine the prevalence of coronary artery disease (CAD) and its risk factors in Karachi, Pakistan. Background: Migrant South Asians residing in the West have one of the highest rates of CAD in the world. Estimates of disease in nonmigrant populations are conflicting. Methods: We conducted a population-based cross-sectional survey on 320 randomly selected adults aged ≥40 years. Coronary artery disease was defined as the composite outcome of (1) abnormalities indicative of definite or probable CAD based on the Minnesota classification of electrocardiogram or (2) past history of heart attack. Results: The overall prevalence of CAD (95% CI) was 26.9% (22.3%-32.0%): 23.7% (17.8%-30.9%) in men vs 30.0% (23.4-37.5%) in women (P = .12). Risks did not differ substantially by age group. The factors (odds ratio, 95% CI) independently associated with CAD were current tobacco use (2.12, 1.21-3.73), systolic blood pressure (1.08, 1.02-1.15, for each 5 mm Hg increase), and proteinuria (2.49, 1.04-5.95). Coronary artery disease odds for women vs men (1.38, 0.84-2.62) increased to 1.60 (0.93-2.75), when adjusted for key risk factors. Conclusions: One in 4 middle-aged adults in Pakistan has prevalent CAD. Risks are uniformly high in the young and in women. Concerted efforts are needed to prevent the epidemic of cardiovascular disease in South Asia, focusing on hypertension, diabetes, smoking, and dyslipidemia.