Few studies have reported changes in rates of overdose after drug misuse treatment. This paper investigates changes in non-fatal overdose between treatment intake and 1 year follow-up among a sample of 753 clients recruited to the National Treatment Outcome Research Study (NTORS). A relatively high rate of overdose (15%) was reported during the 3 months prior to treatment. Variables predictive of overdose at intake to treatment included injecting, frequency of benzodiazepine and cocaine use, quantity of alcohol consumption, and levels of anxiety. At 1 year follow-up, the rate of non-fatal overdose had fallen to 6%. Reduced rates of non-fatal overdose were found for clients treated in both residential and community treatment settings. Reductions in overdose were linked to improvements in frequency of drug use and lower rates of injecting. Clients who overdosed at follow-up showed no improvements in their substance use, except for frequency of crack cocaine use. The risk of non-fatal overdose at 1 year was associated with injecting and multiple drug use. These findings support the view that treatment an important role can play in reducing deaths among drug misusers.