Background and Purpose: Patient-centered care prioritizes patient beliefs and values towards wellbeing. We aimed to map functional status (modified Rankin Scale [mRS] scores) and health-related quality of life on the European Quality of Life 5-dimensional questionnaire (EQ-5D) to derive utility-weighted (UW) stroke outcome measures and test their statistical properties and construct validity. Methods: UW-mRS scores were derived using linear regression, with mRS as a discrete ordinal explanatory response variable in 8 large international acute stroke trials. Linear regression models were used to validate UW-mRS scores by assessing differences in mean UW-mRS scores between the treatment groups of each trial. To explore the variability in EQ-5D between individual mRS categories, we generated receiver operator characteristic curves for EQ-5D to differentiate between sequential mRS categories and misclassification matrix to classify individual patients into a matched mRS category based on the closest UW-mRS value to their observed individual EQ-5D value. Results: Among 22 946 acute stroke patients, derived UW-mRS across mRS scores 0 to 6 were 0.96, 0.83, 0.72, 0.54, 0.22, −0.18, and 0, respectively. Both UW-mRS and ordinal mRS scores captured divergent treatment effects across all 8 acute stroke trials. The sample sizes required to detect the treatment effects using UW-mRS scores as a continuous variable were almost half that required in trials for a binary cut point on the mRS. Area under receiver operator characteristic curves based on EQ-5D utility values varied from 0.66 to 0.81. Misclassification matrix showed moderate agreement between actual and matched mRS scores (kappa, 0.68 [95% CI, 0.67–0.68]). Conclusions: Medical strategies that target avoiding dependency may provide maximum benefit in terms of poststroke health-related quality of life. Despite variable differences with mRS scores, the UW-mRS provides efficiency gains as a smaller sample size is required to detect a treatment effect in acute stroke trials through use of continuous scores. Registration: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT00226096, NCT00716079, NCT01422616, NCT02162017, NCT00120003, NCT02123875. URL: http://ctri.nic.in ; Unique identifier: CTRI/2013/04/003557. URL: https://www.isrctn.com ; Unique identifier: ISRCTN89712435.