Despite a lower prevalence of opioid dependence among females, drug-related problems and risk factors such as prostitution have a negative effect for women in treatment. This study was conducted with the purpose of analyzing gender differences in the German trial on heroin-assisted treatment (HAT), which compared HAT with methadone maintenance treatment (MMT). Significant baseline gender differences were found, with females showing a greater extent of mental distress. Differences in retention and outcome were significant for male patients, but no differences between treatment options were found for female patients. Ongoing prostitution was found to influence drug use outcomes. Other outcome criteria may need to be stressed when assessing the effect of HAT for women.