To determine whether supervised medical prescription of heroin can successfully treat addicts who do not sufficiently benefit from methadone maintenance treatment. Two open label randomised controlled trials. Methadone maintenance programmes in six cities in the Netherlands. 549 heroin addicts. Inhalable heroin (n = 375) or injectable heroin (n = 174) prescribed over 12 months. Heroin (maximum 1000 mg per day) plus methadone (maximum 150 mg per day) compared with methadone alone (maximum 150 mg per day). Psychosocial treatment was offered throughout. Dichotomous, multidomain response index, including validated indicators of physical health, mental status, and social functioning. Adherence was excellent with 12 month outcome data available for 94% of the randomised participants. With intention to treat analysis, 12 month treatment with heroin plus methadone was significantly more effective than treatment with methadone alone in the trial of inhalable heroin (response rate 49.7% v 26.9%; difference 22.8%, 95% confidence interval 11.0% to 34.6%) and in the trial of injectable heroin (55.5% v 31.2%; difference 24.3%, 9.6% to 39.0%). Discontinuation of the coprescribed heroin resulted in a rapid deterioration in 82% (94/115) of those who responded to the coprescribed heroin. The incidence of serious adverse events was similar across treatment conditions. Supervised coprescription of heroin is feasible, more effective, and probably as safe as methadone alone in reducing the many physical, mental, and social problems of treatment resistant heroin addicts.