To assess potential long-term risk factors for major pulmonary embolism, 46 subjects from the Framingham Heart Study with autopsy-confirmed and clinically significant pulmonary embolism were identified in whom age, systolic blood pressure, cholesterol level, cigarette use, glucose level, Metropolitan relative weight, and varicose veins were ascertained at entry into the Study. These variables were compared among these 46 subjects, all 3,470 subjects in whom these variables were measured at the inception of the Study, and the 998 of these subjects who died within 26 years of follow-up. In multivariate analysis of subjects with autopsy-confirmed major pulmonary embolism and all subjects who died, only Metropolitan relative weight was significantly and independently associated with pulmonary embolism and only among women (p less than 0.001). These findings indicate that, in this cohort, increased adiposity in women is an important long-term factor for significant pulmonary embolism at autopsy. This raises the possibility that weight reduction in obese women may decrease the chances of pulmonary embolism.