The aim of this study was to determine the prevalence of recent (last 12 months) depression in regular young heroin users and to ascertain factors associated with depression in this population, broken down by gender. A sample of 561 participants completed a cross-sectional survey. Eligibility criteria were: age 30 years or younger, and having used heroin for at least 12 days in the last 12 months and at least one day in the last 3 months. Participants were recruited outside of health-care facilities in the cities of Barcelona, Madrid and Seville by targeted sampling and chain referral methods. Depression was assessed using the World Mental Health Composite International Diagnostic Interview. The prevalence of recent depression was 22.3% (35.2% among women and 17.3% among men, p<0.001). In the multivariate analysis, the factors positively associated with recent depression in the whole sample were female gender, age 25 or less, inability to work due to health problems and high risk consumption of alcohol. Among woman, the related variables were age 25 or less, cocaine dependence in the last 12 months, and alcohol consumption in that period. Among men, employment status was the only related variable. Analysis of an overall sample without the gender breakdown may hide important differences in the factors associated with depression in men and women. Both prevention and treatment of depression should rely on specific gender analysis.