Background/Aims: Until now, the medical prescription of diamorphine (heroin) has been suggested as suitable for patients who have failed previous maintenance treatments. The aim of this paper is to assess the effects of diamorphine on opioid-dependent patients with no previous maintenance treatment experience (NPME). Methods: The German heroin trial compared diamorphine versus methadone maintenance treatment and included 107 patients with NPME. This paper is a sub-analysis of these patients. Results: When comparing this subsample with the rest of the participants in the study, large baseline differences were found, showing a more severe drug use profile in patients with NPME. However, no differences were found in terms of treatment outcome and treatment retention. In the subsample with NPME, outcome measures on the reduction of illicit drug use were significantly better under diamorphine compared to methadone treatment, while there was no difference in health outcomes. Conclusion: Controlled studies are now necessary to examine whether diamorphine treatment could be considered as one of several options in treating severely opioid-dependent patients, regardless of previous maintenance treatment experience.