['This longitudinal study assessed the changes in drug use patterns and health-related quality of life (HRQL) among HIV-positive drug users in the first methadone maintenance treatment (MMT) cohort in Vietnam.', 'A secondary analysis was conducted on 370 HIV-positive drug users (age: mean ± SD: 29.5 ± 5.9 years; 95.7% men). Modified WHOQOL-BREF, self-report, and opioid confirmatory urine tests were used to assess HRQL and drug use behaviours at baseline, 3, 6, and 9 months. Generalized estimating equations (GEE) models were constructed to adjust for intra-individual correlations.', 'MMT response rate after 9 months was 89.9%. Rates of positive heroin urine tests rapidly decreased at the first trimester (18.1%) and then stabilized during the next 2 trimesters (11.8 and 14.4%). Among patients with continued drug use, frequency of use decreased from 3.4 to 0.7 time/day. Improvements in HRQL were large over the course of the study and highest in the psychological domain. Adjusting for propensity score in GEE models, ongoing heroin use during MMT resulted in large decrements in all HRQL domains.'] Are changes in drug use associated with health-related quality of life improvements among methadone maintenance patients with HIV/AIDS?