PurposeThe purpose of this paper is to examine gender differences in lifetime substance use and non-substance use (non-SUD) psychiatric disorders among illicit drug users and determine factors associated with non-SUD psychiatric disorders independently for males and for females.Design/methodology/approachSecondary analysis of five cross-sectional studies conducted in Barcelona, Spain during 2000-2006. Lifetime DSM-IV substance use and non-SUD psychiatric diagnoses were assessed using the Spanish Psychiatric Research Interview for Substance and Mental disorders (PRISM) among 629 people who use substances (68 per cent male) recruited from treatment (n=304) and out of treatment (n=325) settings. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using binary logistic regression.FindingsThe prevalence of any lifetime psychiatric (non-SUD) disorder was 41.8 per cent, with major depression (17 per cent) and antisocial personality disorder (17 per cent) being the most prevalent disorders. After adjusting for age and study, the odds of having any lifetime non-SUD (OR 2.10; 95%CI 1.48, 2.96); any mood disorder (OR 2.13; 95%CI 1.46, 3.11); any anxiety disorder (OR 1.86; 95%CI 1.19; 2.92); any eating disorder (OR 3.09; 95%CI 1.47, 6.47); or borderline personality disorder (OR 2.30; 95%CI 1.36, 3.84) were greater for females than males. Females were less likely than males to meet criteria for antisocial personality disorder (OR 0.59; 95%CI 0.36, 0.96) and attention deficit disorder (OR 0.37; 95%CI 0.17, 0.78).Research limitations/implicationsPsychiatric disorders are common among people who use substances, with gender differences reported for specific disorders. Gender-sensitive integrated treatment approaches are required to prevent and to address comorbidity psychiatric disorders among this population.Originality/valueThis secondary analysis of five cross-sectional studies included a large sample size allowing sufficient power to examine the differences between men and women. An additional strength of the methodology is the use of the gold standard PRISM which was used to assess disorders.