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Background: Physical variables like mortality or cardiac events were used to evaluate the requirement of red blood cell (RBC) transfusion. However, patient-reported outcomes (PROs) of blood transfusion recipients were seldom assessed. The health-related quality of life (HRQoL) of patients before and after RBC transfusion was compared in this study., Study Design and Methods: The study period was February to June 2016. Standardized generic and anemia symptom-specific HRQoL instruments were administered to patients receiving RBC transfusion in the medical unit of a single center. The primary outcome was the change in HRQoL scores on Days 1 and 7 posttransfusion from baseline values on the day of transfusion (Day 0). Multiple linear regression analysis was performed to study the effect of transfusion strategy and other factors on PRO., Results: The analysis included 99 general medical patients. The median (interquartile range) pretransfusion hemoglobin level was 72 (66-78) g/L. Two or more units of RBCs were prescribed to 45 patients (45%) on Day 0. Functional Assessment of Cancer Therapy-Anemia Subscale improved significantly on Days 1 and 7 by effect sizes of 0.41 and 0.38, respectively (p < 0.001). Regression analysis showed that lower baseline HRQoL scores were associated with better PRO on both Day 1 and Day 7 (p < 0.001). Transfusion trigger and number of RBC units transfused did not affect the change in HRQoL., Conclusion: Worse pretransfusion HRQoL is a predictor of improvement in PRO after blood transfusion. There is no evidence that a restrictive transfusion or single-unit policy jeopardizes PRO., (© 2017 AABB.)