In a retrospective cohort study of 554 hospitalized adults with opioid use disorder (2019–2022), higher early methadone dosing was associated with lower rates of patient-directed discharge (PDD). Among patients receiving methadone within 24 hours of emergency department presentation (n = 325), each additional 10 mg of methadone was associated with reduced odds of PDD at 48 hours (aOR, 0.71), 72 hours (aOR, 0.68), 96 hours (aOR, 0.72), and overall hospitalization (aOR, 0.79). Associations were weaker at 48 hours and nonsignificant at 72 hours. Findings suggest that prompt, adequate methadone treatment may reduce PDD among hospitalized patients with OUD.