Background Epidemiological research is believed to underestimate the lifetime prevalence of mental illness due to recall failure and a lack of rapport between researchers and participants. Method In this prospective study, we examined lifetime prevalence and co-morbidity rates of substance use disorders, antisocial personality disorder (ASPD) and major depressive disorder (MDD) in a representative, statewide Minnesota sample (n=1252) assessed four times between the ages of 17 and 29 years with very low attrition. Results Lifetime prevalence rates of all disorders more than doubled between the ages of 17 and 29 years in both men and women, and our prospective rates at the age of 29 years were consistently higher than rates from leading epidemiological surveys. Although there was some variation, the general trend was for lifetime co-morbidity to increase between the ages of 17 and 29 years, and this trend was significant for MDD-alcohol dependence, MDD-nicotine dependence, and ASPD-nicotine dependence. Conclusions Overall, our results show that emerging adulthood is a high-risk period for the development of mental illness, with increases in the lifetime prevalence and co-morbidity of mental disorders during this time. More than a quarter of individuals had met criteria for MDD and over a fifth had experienced alcohol dependence by the age of 29 years, indicating that mental illness is more common than is estimated in cross-sectional mental health surveys. These findings have important implications for the measurement of economic burden, resource allocation toward mental health services and research, advocacy organizations for the mentally ill, and etiological theories of mental disorders.