Background and aimsUkraine’s Ministry of Health released urgent COVID‐19 guidelines, allowing for early implementation of take‐home dosing (THD) for opioid agonist therapies (OAT) such as methadone. Enrollment in OAT and retention in the program are the most effective HIV prevention strategies for people who inject drugs (PWID). This study aimed to evaluate the impact of Ukraine’s COVID‐19 emergency guidance on OAT treatment enrollment, retention on treatment and mortality.Design and settingUsing Ukraine’s national OAT registry for 252 governmental clinics across 25 regions, we conducted a 12‐month comparative prospective cohort survival analysis. This study compared newly enrolled methadone patients within the initial 6 months following the COVID‐19 guidance (COVID) with patients from the preceding year (pre‐COVID) in a country with high adult HIV prevalence (1.2%) that is concentrated in PWID.ParticipantsIn the nation‐wide sample of newly enrolled PWID in Ukraine, comprising 2798 individuals, 1423 were in the COVID cohort and 1375 were in the pre‐COVID cohort. The majority were male (86.7%), with an average age of 39.3 years.MeasurementsPrimary outcomes were average monthly enrollment per cohort, treatment retention and mortality, with internal time‐dependent predictors, including THD and optimal (> 85 mg) methadone dosing.ResultsRelative to the pre‐COVID period, the monthly average patient enrollment was statistically significantly higher during the COVID period (283.7 versus 236.0; P < 0.0001), where patients were more likely to transition to THD and achieve optimal dosing earlier. Significant differences were observed in the proportions of person‐months on THD (41 versus 13%, P < 0.0001) and optimal dosing (38 versus 31%, P < 0.0001) between the COVID and pre‐COVID cohorts. Predictors of treatment retention, expressed as adjusted hazard ratios (aHR), included early THD [aHR = 1.90, 95% confidence interval (CI) = 1.47–2.45], early optimal dosing (aHR = 1.71, 95% CI = 1.37–2.13) and prior methadone treatment (aHR = 1.39, 95% CI = 1.15–1.68). These factors persisted, respectively, in the pre‐COVID (aHR = 2.28, 95% CI = 1.41–3.70; aHR = 1.84, 95% CI = 1.32–2.56; and aHR = 1.36, 95% CI = 1.06–1.74) and COVID (aHR = 1.91, 95% CI = 1.40–2.59; aHR = 1.61, 95% CI = 1.20–2.16; and aHR = 1.49, 95% CI = 1.08–1.94) cohorts. Survival did not differ significantly between the two prospective cohorts.ConclusionUkraine’s prompt adoption of early take‐home dosing for opioid agonist therapies, such as methadone, following the emergency COVID‐19 guidance appears to have increased enrollment into methadone and improved treatment retention for people who inject drugs without adverse effects on patient survival.