Objective: To evaluate the association between functional measures at admission to acute inpatient rehabilitation (AIR) and health-related quality of life (HRQOL) scores at 3 months after ischemic stroke. Design: Consecutive patients with ischemic stroke admitted to AIR were consented to a prospective registry. Setting: Large academic referral inpatient rehabilitation hospital. Participants: Patients (N=113) with ischemic stroke (mean age 70.6 ± 14.5y; 54.0% male; 56.6% white) were included in the analysis. Interventions: Not applicable. Main Outcome Measures: Admission FIM and Berg Balance Scores (BBS) were abstracted when available. The Neuro-Quality of Life questionnaire was used to assess 3-month HRQOL in 4 domains: upper extremity (UE), lower extremity (LE), executive functions (EF), and general concerns (GC). Associations of FIM and BBS scores with impaired HRQOL at 3 months were evaluated. Results: The median time from stroke onset to admission FIM and BBS was 6.4 (interquartile range [IQR] 4.2-11.3) and 8.9 (IQR 5.8-14.4) days, respectively. A 5-point increase in admission FIM score decreased the likelihood of impairment in HRQOL at 3 months by 25% for GC (odds ratio [OR] 0.75, 95% confidence interval [CI] 0.61-0.93, P=.01), 31% for EF (OR 0.69, 95% CI 0.56-0.85, P=.001), 16% for UE function (OR 0.84, 95% CI 0.73-0.96, P=.01), and 21% for LE function (OR 0.79, 95% CI 0.67-0.93 P=.004). A 5-point increase in admission BBS decreased the likelihood of impairment in HRQOL domains at 3 months by 15% for UE function (OR 0.85, 95% CI 0.75-0.98, P=.02) and 25% for LE function (OR 0.75, 95% CI 0.64-0.89, P=.001). Conclusions: Admission FIM and BBS were strongly associated with 3-month HRQOL associated across multiple domains following stroke. These findings indicate that HRQOL can be predicted earlier in a patient's course during AIR.