Female drug users report greater psychopathology and risk behaviours than male drug users, putting them at greater risk for HIV. This mixed-methods study determined psychiatric, behavioural and social risk factors for HIV among 118 female drug users (27% (32/118) were HIV seropositive) in Barcelona. DSM-IV disorders were assessed using the Spanish Psychiatric Research Interview for Substance and Mental Disorders. 30 participants were interviewed in-depth. In stepwise multiple backward logistic regression, ever injected with a used syringe, antisocial personality disorder, had an HIV seropositive sexual partner and substance-induced major depressive disorder were associated with HIV seropositivity. Qualitative findings illustrate the complex ways in which psychiatric disorders and male drug-using partners interact with these risk factors. Interventions should address all aspects of female drug users' lives to reduce HIV.