Several reports express concern at the mortality associated with the use of oral naltrexone for opiate dependency. Registry controlled follow-up of patients treated with naltrexone implant and buprenorphine was performed. In the study, 255 naltrexone implant patients were followed for a mean (+/- standard deviation) of 5.22 +/- 1.87 years and 2,518 buprenorphine patients were followed for a mean (+/- standard deviation) of 3.19 +/- 1.61 years, accruing 1,332.22 and 8,030.02 patient-years of follow-up, respectively. The crude mortality rates were 3.00 and 5.35 per 1,000 patient-years, respectively, and the age standardized mortality rate ratio for naltrexone compared to buprenorphine was 0.676 (95% confidence interval = 0.014 to 1.338). Most sex, treatment group, and age comparisons significantly favored the naltrexone implant group. Mortality rates were shown to be comparable to, and intermediate between, published mortality rates of an age-standardized methadone treated cohort and the Australian population. These data suggest that the mortality rate from naltrexone implant is comparable to that of buprenorphine, methadone, and the Australian population.