Understanding the impact of prior substance misuse on emergent health problems is important to the implementation of effective preventive care. This study examined the 5-year incidence rates using a sample of middle-aged adult adoptees (N = 309, mean(age) = 44.32, standard deviation(age) = 7.28). Subjects reported on health problems at two waves of study. DSM-IV diagnoses of substance misuse were obtained using a semi-structured diagnostic interview. Finally, health services utilization and perceived health status were collected. Lifetime diagnoses of marijuana and other non-marijuana substance misuse significantly predicted new occurrences of cardiovascular and metabolic disease. Alcohol misuse predicted earlier onset of cardiovascular disease among men. Marijuana and other non-marijuana drugs predicted earlier onset of cardiovascular disease for men and women. Finally, marijuana and other non-marijuana drugs predicted earlier onset of metabolic disease among men. Substance misuse did not predict health services utilization despite higher rates of disease. These findings emphasize the need to assess lifetime substance misuse when evaluating health risks associated with use.