The present study evaluates the effectiveness of low-threshold methadone maintenance in reducing overdose mortality. In a prospective cohort study conducted in Amsterdam, 498 Dutch injecting drug users (IDU) provided 1,969 person years of follow-up (1989-1995). Forty-four IDU died in this period, 15 due to illicit drug overdose. Compared to IDU not in maintenance, the adjusted relative risk for overdose mortality among those receiving 5-50 mg, 55-70 mg, and 75+ mg were 0.35, 0.13, and 0.11, respectively (p < .05). Also current injection use and HIV-seropositivity were independent predictors for overdose mortality. Whereas previous studies indicated effectiveness of methadone-assisted detoxification and high-dose maintenance programs in reducing mortality, the present study findings suggest that low-threshold maintenance programs also reduce overdose mortality, with higher dosages being most protective.