BACKGROUND Ukraine's volatile syndemics of tuberculosis (TB) and HIV among people who inject drugs (PWIDs) introduces numerous treatment challenges for each condition, including high mortality and development of multi-drug resistant TB (MDR-TB). METHODS A prospective, non-randomized 90-day observational study was conducted in six Ukrainian TB treatment sites to assess the effectiveness of integrating methadone maintenance (MMT) with TB treatment using: (1) 90-day TB treatment retention; (2) time to treatment discontinuation; (3) TB medication adherence; and (4) subject disposition, including mortality. Of the 110 participants enrolled, 57 received MMT and 53 did not (non-MMT). RESULTS All of the primary outcomes were significantly better in MMT versus non-MMT groups, including 90-day TB treatment completion (89.5% versus 73.6%; p=0.031), time to TB treatment discontinuation (p=0.039) and TB medication adherence (97.1% versus 86.2%; p<0.001) after controlling for death. The major reasons for treatment non-completion in the non-MMT group included death (N=3), administrative discharge from the clinic (N=5), loss to follow-up (N=2), and arrest (N=4). Overall, 90-day mortality was high (8.2%). After controlling for covariates differing between the two groups at baseline, the only independent predictor of completing 90 days of TB treatment was receipt of MMT in an integrated treatment setting (AOR=3.05; 95% CI 1.08-8.66). CONCLUSIONS MMT integrated into inpatient TB treatment significantly improves retention in TB treatment and TB medication adherence among PWIDs. These findings call for policy change to increase the number of MMT sites in TB facilities and make MMT a low-threshold treatment option for opioid dependence in Ukraine.