This study compared the safety and efficacy of sublingual buprenorphine tablets with oral methadone in a population of opioid-dependent individuals in a double-blind, randomized, 6-week trial using a flexible dosing procedure. Fifty-eight patients seeking treatment for opioid dependence were recruited in three outpatient facilities and randomly assigned to substitution with buprenorphine or methadone. The retention rate was significantly better in the methadone maintained group (90 vs. 56%; P<0.001). Subjects completing the study in both the treatment groups had similar proportions of opioid positive urine samples (buprenorphine 62%; methadone 59%) and positive urine specimens, as well as mean heroin craving scores decreased significantly over time (P=0.035 and P<0.001). The proportion of cocaine-positive toxicology results did not differ between groups. At week six mean stabilization doses were 10.5 mg per day for the sublingual buprenorphine tablet, and 69.8 mg per day for methadone, respectively. Patient performance during maintenance was similar in both the groups. The high attrition rate in the buprenorphine group during the induction phase might reflect inadequate induction doses. Thus, buprenorphine is a viable alternative for methadone in short-term maintenance treatment for heroin dependence if treatment induction is done with adequate dosages.