This study examines gender differences in the association of lifetime mental and substance use disorders among individuals with opioid use disorders in the United States. The sample (N=578) is from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), which is a representative household survey. Bivariate analyses and logistic regression modeling were conducted. About 70% of the sample had a lifetime non-substance use Axis I disorder; women were about twice as likely as men to have either a mood or anxiety disorder. About half of the sample had a personality disorder, with women more likely to have paranoid disorder and men more likely to have antisocial personality disorder. Individuals with a lifetime mental disorder were about three times more likely than others to be dependent on other substances, independent of gender. The study demonstrated an inverse relationship between lifetime mental and other substance use disorders, with women having significantly higher odds for several of the mental disorders and men having greater odds of other substance use disorders.