Abstract Background Cession of heroin use may be followed by a protracted-abstinence (PA) syndrome consisting of craving, negative mood, and physiological changes. PA symptoms have rarely been compared between drug-free and methadone-maintained former heroin users after similar lengths of heroin abstinence. Methods Seventy former heroin users were included in one of four groups: in day 15–45 of methadone maintenance therapy (short-term MMT), in month 5–6 of MMT (long-term MMT), opiate-free for 15–45 days after methadone-assisted heroin detoxification (short-term post-methadone), and opiate-free for 5–6 months after methadone-assisted heroin detoxification (long-term post-methadone). PA symptoms (negative mood, dyssomnia, somatization, and craving), and blood pressure and pulse were assessed pre- and post-neutral videotape and pre- and post-heroin videotape. Results Dyssomnia and the total PA score were worst in short-term post-methadone participants, mood was best in long-term MMT participants, and cue-induced craving was least severe in long-term MMT participants. Blood pressure and pulse did not differ across groups. Conclusions Even after acute withdrawal, the first months of heroin abstinence after methadone-assisted detoxification may be more difficult in terms of cue-induced craving and other PA symptoms than the first months of heroin abstinence during MMT. Our findings add to the literature supporting MMT for prevention of cue-induced heroin craving.