Background Treatment with medications for opioid use disorder (MOUD) may improve hepatitis C virus (HCV) treatment outcomes by providing additional contact with health care professionals to support patient engagement. Objective: We describe a pharmacist-led HCV treatment model and assessed the effect of MOUD on adherence to direct-acting antivirals (DAAs) in an underserved patient population. Methods: This was a retrospective cohort study of adults (age≥18 years) treated for HCV infection with DAAs at a Federally Qualified Health Center in Portland, Oregon, between March 1, 2019, and March 16, 2020. Patients were followed to 12 weeks to assess adherence to DAAs by MOUD status. Results: Among 59 eligible patients, 16 (27%) were prescribed MOUD. Baseline characteristics were similar between patients who did and did not receive MOUD. Adherence to DAAs was overall high and not significantly different between the groups (median: 98.5% vs median: 100%; P = .06). Five patients missed at least one dose due to an adverse drug effect and two of these patients discontinued HCV therapy due to these effects. Conclusion: Adherence to HCV therapy was nearly 100% among underserved patients in a pharmacist-led HCV treatment model and did not differ by MOUD engagement.