Estrogen receptors (ESR) 1 and 2 are expressed in the normal and atherosclerotic arteries mediating the atheroprotective action of estrogen to artery wall cells. Whether variants of these receptor genes associate with autopsy-verified coronary artery wall atherosclerosis is not known. This study investigated whether variants of the ESR1 gene are associated with autopsy-verified coronary artery wall atherosclerosis and thrombosis. Coronary arteries were taken from 300 white Finnish male autopsy cases aged 33-69 years included in the Helsinki Sudden Death Study. Areas of coronary wall covered with fatty streaks, fibrotic, calcified, and complicated lesions were measured using computer-assisted planimetry and related to ESR1 PvuII genotypes (P/P, P/p, and p/p) determined by PCR. The mean area of complicated lesions of three major coronaries and the presence of coronary thrombosis were significantly associated with the ESR1 genotype in men aged 53 years or older (median age as a cut off point). No such association was found in men aged under 53 years. After adjusting for age and body mass index the men aged 53 years or over with P/p and P/P genotype had areas of complicated lesions on average two- and fivefold larger than subjects with the p/p genotype. The age and body mass index adjusted odds ratios for coronary thrombosis were 6.2 for P/p and 10.6 for P/P compared to men with the p/p genotype. After additional adjustment for diabetes and hypertension the ESR1 genotype persisted as an independent predictor of complicated lesions ( P=0.007) and coronary thrombosis. In conclusion, the ESR1 gene is a potential candidate behind the pathogenesis of acute coronary events.