The objectives of the present study were to estimate the psychiatric comorbidity of Taiwanese heroin users seeking treatment and to identify the gender differences in psychiatric comorbidity and drug use behavior. Subjects were interviewed using a structured questionnaire on drug use behavior and the Mini International Neuropsychiatric Interview for psychiatric disorders. Of the subjects, 58.5% of the male and 62.5% of the female subjects had at least one non-substance-use axis I psychiatric disorder or antisocial personality disorder. Compared to male subjects, female subjects were younger, were less educated, had higher rates of unemployment and had earlier onset of illicit drug use. Female subjects were 11-fold more likely than male subjects to exhibit suicidal behavior. Among heroin abusers in the present study, female subjects were more widely exposed to unfavorable social factors and had substantially higher incidence of suicidal behavior than male subjects. Drug treatment centers should be aware of these gender differences and pay particular attention to comorbid depressive disorders and suicidal behavior of female heroin abusers.