The efficacy and effectiveness of methadone maintenance treatment (MMT) in the medical management of opioid addiction has been well-established, but treatment outcomes are compromised by the continued use of licit and illicit drugs during MMT. The present study examined the relationship between in-treatment illicit drug use and retention and dropout of 604 MMT patients in Washington, D.C. Sixty-eight percent of patients did not test positive for an unprescribed drug during the study period. Of patients who tested positive for an illicit drug during the baseline period, 55% tested positive for cocaine, 44% for opiates, 23% for THC, 20% for benzodiazepines, 7% for PCP, and 4% for amphetamines. Those testing positive were three times more likely to leave treatment than those who did not test positive. Testing positive for one drug doubled the rate of attrition; testing positive for multiple drugs quadrupled the risk of attrition. Non-prescribed opioid or benzodiazepine use was a predictor of MMT dropout, but prescribed opioid or benzodiazepine use was not. Continued illicit drug use poses significant risk for subsequent premature termination of MMT. Assertive clinical management of continued illicit drug use could provide mechanisms to enhance MMT retention and long-term recovery outcomes.