AIM: To determine whether buprenorphine is more effective than clonidine and other symptomatic medications in managing ambulatory heroin withdrawal. DESIGN: Open label, prospective randomized controlled trial examining withdrawal and 4-week postwithdrawal outcomes on intention-to-treat. SETTING: Two specialist, out-patient drug treatment centres in inner city Melbourne and Sydney, Australia. PARTICIPANTS: One hundred and fourteen dependent heroin users were recruited. Participants were 18 years or over, and with no significant other drug dependence, medical or psychiatric conditions or recent methadone treatment. One hundred and one (89%) participants completed a day 8 research interview examining withdrawal outcomes, and 92 (81%) completed day 35 research interview examining postwithdrawal outcomes. INTERVENTIONS: Participants randomized to control (n = 56) (up to 8 days of clonidine and other symptomatic medications) or experimental (n = 58) (up to 5 days of buprenorphine) withdrawal groups. Following the 8-day withdrawal episode, participants could self-select from range of postwithdrawal options (naltrexone, substitution maintenance, or counselling). MEASUREMENTS: Retention in withdrawal; heroin use during withdrawal; and retention in drug treatment 4 weeks after withdrawal. SECONDARY OUTCOMES: Withdrawal severity; adverse events, and heroin use in the postwithdrawal period. FINDINGS: The experimental group had better treatment retention at day 8 (86% versus 57%, P = 0.001, 95% CI for numbers needed to treat (NNT) = 3-8) and day 35 (62% versus 39%, P = 0.02, 95% CI for NNT = 4-18); used heroin on fewer days during the withdrawal programme (2.6 +/- 2.5 versus 4.5 +/- 2.3, P < 0.001, 95% CI = 1-2.5 days) and in the postwithdrawal period (9.0 +/- 8.2 versus 14.6 +/- 10, P < 0.01, 95% CI = 1.8-9.4); and reported less withdrawal severity. No severe adverse events reported. CONCLUSIONS: Buprenorphine is effective for short-term ambulatory heroin withdrawal, with greater retention, less heroin use and less withdrawal discomfort during withdrawal; and increased postwithdrawal treatment retention than symptomatic medications.