Objectives. We explored the relationship between boarded-up housing and rates of gonorrhea and premature mortality. Methods. In this ecological study of 107 US cities, we developed several models predicting rates of gonorrhea and premature death before age 65 from all causes and from specific causes. We controlled for race, poverty, education, population change, and health insurance coverage. Results. Boarded-up housing remained a predictor of gonorrhea rates, all-cause premature mortality, and premature mortality due to malignant neoplasms, diabetes, homicide, and suicide after control for sociodemographic factors. Conclusions. Boarded-up housing may be related to mortality risk because of its potential adverse impact on social relationships and opportunities to engage in healthful behaviors. Neighborhood physical conditions deserve further consideration as a potential global factor influencing health and well-being.