INTRODUCTION: People with opioid use disorder (OUD) have high rates of discharge against medical advice from the hospital. Interventions for addressing these patient-directed discharges (PDDs) are lacking. We sought to explore the impact of methadone treatment for OUD on PDD. METHODS: Using electronic record and billing data from an urban safety-net hospital, we retrospectively examined the first hospitalization on a general medicine service for adults with OUD from January 2016 through June 2018. Associations with PDD compared to planned discharge were examined using multivariable logistic regression. Administration patterns of maintenance therapy versus new in-hospital initiation of methadone were examined using bivariate tests. RESULTS: During the study time period, 1,195 patients with OUD were hospitalized. 60.6% of patients received medication for OUD, of which 92.8% was methadone. Patients who received no treatment for OUD had a 19.1% PDD rate while patients initiated on methadone in-hospital had a 20.5% PDD rate and patients on maintenance methadone during the hospitalization had a 8.6% PDD rate. In multivariable logistic regression, methadone maintenance was associated with lower odds of PDD compared to no treatment (aOR 0.53, 95% CI 0.34-0.81), while methadone initiation was not (aOR 0.89, 95% CI 0.56-1.39). About 60% of patients initiated on methadone received 30 mg or less per day. CONCLUSIONS: In this study sample, maintenance methadone was associated with nearly a 50% reduction in the odds of PDD. More research is needed to assess the impact of higher hospital methadone initiation dosing on PDD and if there is an optimal protective dose.