OBJECTIVE: The aim of this study was to compare the prevalence and comorbidity patterns of psychiatric disorders in subjects making medically serious suicide attempts and in comparison subjects. METHOD: The association between mental disorders and the risk of a suicide attempt was examined in 302 consecutive individuals who made serious suicide attempts and 1,028 randomly selected comparison subjects. Each subject completed a semistructured interview, and a significant other underwent a parallel interview; best-estimate DSM-III-R diagnoses were then generated. RESULTS: Of those who made serious suicide attempts, 90.1% had a mental disorder at the time of the attempt. Multiple logistic regression showed that those who made suicide attempts had high rates of mood disorders (odds ratio = 33.4, 95% confidence interval = 21.9-1.2); substance use disorders (odds ratio = 2.6, 95% confidence interval = 1.6-4.3); conduct disorder or antisocial personality disorder (odds ratio = 3.7, 95% confidence interval = 2.1- 6.5); and nonaffective psychosis (odds ratio = 16.8, 95% confidence interval = 2.7-105.8). The relationship between psychiatric morbidity and suicide risk varied with age and gender. The incidence of comorbidity was high: 56.6% of those who made serious suicide attempts had two or more disorders. The risk of a suicide attempt increased with increasing psychiatric morbidity: subjects with two or more disorders had odds of serious suicide attempts that were 89.7 times the odds of those with no psychiatric disorder. CONCLUSIONS: Individuals who made serious suicide attempts had high rates of mental disorders and of comorbid disorders. Subjects with high levels of psychiatric comorbidity had markedly high risks of serious suicide attempts.