OBJECTIVES: Myeloproliferative neoplasm (MPN)-associated myelofibrosis is a cancer in which anemia is common.  The Functional Assessment of Cancer Therapy (FACT) –Anemia instrument measures general quality of life (QOL) and anemia-related concerns of people with cancer. We assessed the relationship between anemia response to therapy with pomalidomide and domains of the FACT-An instrument. METHODS:  Data were from a phase-2 randomized double-blind Bayesian “pick-the-winner” trial of pomalidomide and prednisone in subjects with MPN-associated myelofibrosis and anemia (including RBC-transfusion-dependence).  Details of the study, including definitions of anemia response, RBC-transfusion-dependence and –independence are reported. Change in QOL from randomization to the last cycle of therapy was evaluated using the FACT-An physical well-being (PWB), functional well-being (FWB), trial outcome index (TOI) and anemia (An) domains.  Minimally clinically important differences (MID) were used to determine the smallest difference in scores which subjects perceived as beneficial in the FACT-An domains of interest.  Subjects were classified as meeting MID for responsiveness if their change score from baseline was greater than one standard error of measurement (SEM) indicating improvement. RESULTS:  Eighty-five subjects were studied.  All FACT-An domains showed strong reliability as measured by Cronbach alpha (PWB α=0.77, FWB α=0.87, An α=0.92, TOI α=0.95). Thirty-one subjects were classified as anemia responders by clinical and laboratory criteria.  Anemia responders showed greater improvement in PWB, FWB and TOI scores than non-responders across all FACT-An domains. Improvement began at the second 28 day cycle of therapy and was sustained. CONCLUSIONS:   We show anemia response correlates with improved QOL measured by the FACT-An instrument in persons with MPN-associated myelofibrosis receiving pomalidomide.