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Introduction: Limited data exists for inpatient rehabilitation outcomes predicting health-related quality of life (HRQOL) in stroke patients. We evaluated the association between Functional Independence Measure (FIM) scores during inpatient rehabilitation and HRQOL scores at 3 months.Methods: Between 2012 and 2014, consecutive patients admitted to an inpatient rehabilitation hospital with ischemic stroke were consented in a prospective registry with 3-month follow-up. The admission FIM score were recorded. The Neuro-QOL questionnaire was used to assess 3-month HRQOL in 4 domains: upper extremity (UE), lower extremity (LE), executive functions (EF), and general concerns (GC). Impaired HRQOL was defined as T-scores <45 for each domain. We analyzed the unadjusted and adjusted association between FIM scores and impaired HRQOL.Results: One-hundred thirteen patients (mean age 67.3±15.8 years; 50% male; 56.6% white) were included in final analysis. The median time from stroke onset to admission FIM score was 7 days (IQR 4.6-12.4). Median FIM score was 51 points (IQR 35-62). On unadjusted analysis, a 1-point increase in admission FIM scores resulted in less likelihood of impaired 3-month HRQOL domains: 6% for GC (OR 0.94, 95% CI 0.91-0.98, p<0.001), 7% for EF (OR 0.93, 95% CI 0.90-0.96 p<0.001), 4% for LE function (OR 0.96, 95% CI 0.93-0.98, p=0.001), and 3% for UE function (OR 0.97, 95% CI 0.95-0.99, p=0.01). In analyses adjusting for age, sex, time from stroke to FIM evaluation, race, baseline mRS, initial NIHSS, insurance, past medical history (atrial fibrillation, hypertension, renal disease, diabetes mellitus, cardiac disease, and prior stroke), a 1-point increase in admission FIM scores had similar effects on HRQOL domains: 6% for GC (OR 0.94, 95% CI 0.91-0.99, p=0.01), 7% for EF (OR 0.93, 95% CI 0.89-0.97 p=0.001), 5% for LE function (OR 0.95, 95% CI 0.92-0.99, p=0.004), and 3% for UE function (OR 0.97, 95% CI 0.94-0.99, p=0.01).Conclusions: There is a strong association between FIM scores at admission to inpatient rehabilitation and 3-month HRQOL across multiple HRQOL domains. These findings indicate that long-term HRQOL can be predicted earlier in a patient’s course during inpatient rehabilitation.