Prescription opioid use has grown rapidly, but few studies examined whether users have similar treatment responses as heroin users. Participants were 1,648 opioid users in Florida Access to Recovery (2004-2007). Participants engaged in methadone or buprenorphine maintenance had better retention than those in nonmaintenance treatment. Heroin only users (HO) had better engagement in nonmaintenance treatments and had worse retention than prescription opioid only users (PO). In methadone maintenance, PO were more likely to report opioid abstinence during treatment than heroin and prescription opioid users (H&P). Future research should focus on understanding and improving the treatment experience of opioid use subgroups.