We sought to examine whether methadone maintenance therapy (MMT) decreased rates of antiretroviral therapy (ART) discontinuation and was associated with plasma HIV RNA responses among a cohort of illicit drug users. Cumulative ART discontinuation rates were estimated using Kaplan-Meier methods and factors independently associated with ART discontinuation were identified using Cox proportional hazards regression. Engagement in MMT was negatively and independently associated with ART discontinuation [Adjusted Relative Hazard = 0.67 (95 % CI 0.54-0.83); p < 0.001]. Among participants receiving ART and MMT, 81.6 % of plasma HIV-1 RNA assessments were <500 copies/mL, while 65.81 % of HIV-1 RNA assessments among those prescribed ART without MMT were <500 copies/mL (p < 0.001). These results demonstrate that engagement in MMT conferred a protective benefit against ART discontinuation and was associated with a significant increase in plasma HIV RNA suppression among HIV-infected opioid-dependent drug users.