OBJECTIVE There is controversy about the role of positive family history as an independent risk factor for coronary artery disease. The aim of this work was to investigate the influence of family history on presentation of coronary artery disease in adult offspring, and on its severity. METHODS In a retrospective cross-sectional study at Tehran Heart Center (University of Tehran Medical Sciences), 6399 patients with established coronary artery disease who underwent coronary angiography for standard indications were assessed. Coronary artery disease was defined as atherosclerotic involvement of more than 50% in at least one major coronary artery. RESULTS 953 patients (14.9%) had a verified positive family history of coronary artery disease, of whom 193 patients (20.2%) and 215 patients (22.5%) had paternal and maternal positive history, respectively. The mean age of clinical onset of ischemic heart disease in patients with a positive history was significantly lower than patients with no history (p < 0.001). Left main coronary lesion was significantly more frequent in patients with positive history (p = 0.017). Multivariate logistic regression analysis demonstrated that presentation of coronary artery disease in the form of acute coronary syndrome was significantly more prevalent in the background of positive family history (odds ratio, OR = 1.44, 95% confidence interval, CI: 1.14-1.83, p = 0.002), especially above 45 years old. CONCLUSIONS These findings indicate that positive family history is a major risk factor for coronary artery disease which strongly predisposes to the atherosclerotic process at younger ages; therefore, these patients should be evaluated and managed more intensively for other risk factors.