Abstract Background and Objectives Opioid use has been linked to increased stroke incidence and severity; however, data on effects during acute stroke hospitalization are limited. Methods We used the 2016–2020 National Inpatient Sample to evaluate the effects of opioid disorders on patient‐directed discharge (PDD) and length of stay (LOS) in 3,101,545 patients. Results On multivariate analysis, opioid disorders were independently associated with discharge AMA (aOR: 2.29; 95% CI: 1.98–2.65) and longer LOS (β: 1.5, SE: 0.138; p < .001). Discussion and Conclusions Opioid disorders may predispose PDD and prolonged hospital courses in stroke admissions. Scientific Significance Opioid disorders may warrant targeted inpatient management and health system planning in stroke.