The aim of this naturalistic (observational) controlled cohort study was to compare the long-term outcomes of treatment-resistant heroin addicts with (HA+BZD) and without (HA-BZD) comorbid benzodiazepine (BZD) severe addiction. Methods. 63 HA-BZD and 14 HA+BZD patients were monitored prospectively along an enhanced methadone maintenance treatment programme (MMTP). HA+BZD patients were treated, also, with clonazepam maintenance treatment (CMT). Results. Survival-in-treatment rates were no different in HA+BZD and HA-BZD patients. HA+BZD patients showed better outcome results than HA-BZD patients. HA+BZD patients needed a higher methadone dosage in the stabilization phase. Conclusions. This study supports the possibility to use methadone maintenance and clonazepam maintenance combination in heroin-addicted patients with comorbid severe BZD dependence.