Background There are increasing concerns regarding pharmaceutical opioid harms including overdose and dependence, with an associated increase in treatment demand. People dependent on pharmaceutical opioids appear to differ in important ways from people who use heroin, yet most opioid agonist treatment research has been conducted in people who use heroin. Objectives To assess the effects of maintenance agonist pharmacotherapy for the treatment of pharmaceutical opioid dependence. Search methods The search included the Cochrane Drugs and Alcohol Group's Specialised Register of Trials; the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 5); PubMed (January 1966 to May 2015); EMBASE (Ovid) (January 1974 to May 2015); CINAHL (EBSCOhost) (1982 to May 2015); ISI Web of Science (to May 2014); and PsycINFO (Ovid) (1806 to May 2014). Selection criteria We included randomised controlled trials examining maintenance opioid agonist treatments that made the following two comparisons: 1. full opioid agonists (methadone, morphine, oxycodone, levo‐alpha‐acetylmethadol (LAAM), or codeine) versus different full opioid agonists or partial opioid agonists (buprenorphine) for maintenance treatment and 2. full or partial opioid agonist maintenance versus placebo, detoxification only, or psychological treatment (without opioid agonist treatment). Data collection and analysis We used standard Cochrane methodological procedures. Main results We identified six randomised controlled trials that met inclusion criteria (607 participants). We found moderate quality evidence from two studies of no difference between methadone and buprenorphine in self reported opioid use (risk ratio (RR) 0.37, 95% confidence interval (CI) 0.08 to 1.63) or opioid positive urine drug tests (RR 0.81, 95% CI 0.56 to 1.18). There was low quality evidence from three studies of no difference in retention between buprenorphine and methadone maintenance treatment (RR 0.69, 95% CI 0.39 to 1.22). There was moderate quality evidence from two studies of no difference between methadone and buprenorphine on adverse events (RR 1.10, 95% CI 0.64 to 1.91). We found low quality evidence from three studies favouring maintenance buprenorphine treatment over detoxification or psychological treatment in terms of fewer opioid positive urine drug tests (RR 0.63, 95% CI 0.43 to 0.91) and self reported opioid use in the past 30 days (RR 0.54, 95% CI 0.31 to 0.93). There was no difference on days of unsanctioned opioid use (standardised mean difference (SMD) ‐0.31, 95% CI ‐0.66 to 0.04). There was moderate quality evidence favouring buprenorphine maintenance over detoxification or psychological treatment on retention in treatment (RR 0.33, 95% CI 0.23 to 0.47). There was moderate quality evidence favouring buprenorphine maintenance over detoxification or psychological treatment on adverse events (RR 0.19, 95% CI 0.06 to 0.57). The main weaknesses in the quality of the data was the use of open‐label study designs. Authors' conclusions There was low to moderate quality evidence supporting the use of maintenance agonist pharmacotherapy for pharmaceutical opioid dependence. Methadone or buprenorphine appeared equally effective. Maintenance treatment with buprenorphine appeared more effective than detoxification or psychological treatments. Due to the overall low to moderate quality of the evidence and small sample sizes, there is the possibility that the further research may change these findings.