We identified methadone maintenance therapy (MMT) use during follow-up interviews and examined associations between MMT use and socio-demographic and drug-related variables using generalized estimating equations (GEE). Of the 1587 participants recruited into this cohort, 170 (11%) were enrolled in MMT at baseline and additional 498 (31%) initiated MMT during follow-up. Of those ever enrolled in MMT, 406 (61%) ceased MMT and re-initiated MMT on more than one occasion. The median treatment duration was 14.4 months. Factors that were negatively and significantly associated with MMT use in multivariate analyses included: Aboriginal ethnicity (adjusted odds ratio [AOR] = 0.40); recent incarceration (AOR = 0.79); sex trade involvement (AOR = 0.87); syringe lending (AOR = 0.72); heroin injection (AOR = 0.64), whereas female gender (AOR = 2.47), HIV positivity (AOR = 1.57), and crack cocaine smoking (AOR = 1.23) were positively and significantly associated with being on MMT. Unstable housing, syringe borrowing, non-fatal overdose, cocaine injection, and residence in Vancouver's Downtown Eastside were not associated with MMT use in multivariate analyses. Our study demonstrates high rates of initiation of and retention in MMT among local IDUs. While the use of MMT was associated with reductions in heroin use and HIV risk behavior, barriers to Aboriginal IDUs were evident, and the association with increased crack cocaine use deserves further study.