Background: MF is associated with substantial symptom burden that can negatively impact pt quality of life (QOL). Transfusions may reduce anemia-associated symptoms, but can be burdensome and carry complications that may affect social, emotional, and general health; thus, QOL may be further negatively affected in transfusion-dependent (TD) pts. To characterize the relationship between transfusion burden and pt-reported outcomes (PROs), we report an exploratory post hoc analysis of the phase 3 S1 and S2 trials of the JAK1/JAK2/ACVR1 inhibitor momelotinib (MMB) in pts with MF. Methods: The pooled analysis set comprised both arms of the intent-to-treat populations of S1 (JAK inhibitor naive, MMB vs ruxolitinib [RUX]; N = 432) and S2 (JAK inhibitor exposed, MMB vs best available therapy [88% RUX]; N = 156). Transfusion independent (TI): no transfusions and hemoglobin (Hb) ≥8 g/dL in 12 wk; TD: ≥4 units transfused or Hb < 8 g/dL in 8 wk; transfusion requiring (TR): not meeting TI or TD criteria. PRO assessment: SF-36v2 (physical functioning [PF], role-physical [RP], general health [GH], vitality [VT], social functioning [SF], and mental health [MH] domains; norm-based scores [NBS] range from 11.6 to 70.4 based on domain). PROs by transfusion status were described over the 24-wk randomized period. Results: SF-36v2 NBS were available from 503/588 pts in the pooled analysis set at baseline (BL); mean NBS in all domains were lower than the general population mean per the SF-36v2 Manual (50; SD, 10): PF, 39.6; RP, 39.0; GH, 39.8; VT, 43.6; SF, 43.2; MH, 46.3. Within the pooled analysis set, mean NBS in all domains at BL and week 24 (W24) were lower in TD vs TI pts. Among BL TD pts (n = 150) at W24, 75 remained TD (TD-TD), 40 became TI (TD-TI), 21 became TR, and 14 had no data. Pts who became TI experienced greater improvement (positive mean change from BL) in most domains vs pts who remained TD (Table). Conclusions: Among pts with MF in S1 and S2, TD pts had lower functioning and HRQOL than TI pts across SF-36v2 domains, suggesting that transfusion dependence has detrimental effects on multiple aspects of QOL. Among BL TD pts, those who became TI at W24 had greater improvement across most domains than those who remained TD, with mean changes for TD-TI pts near or above the minimally important difference (2 or 3, based on domain) for groups with low BL NBS. These analyses highlight transfusion dependence as a key pt-centered outcome and support further research into the impact of transfusions on QOL in MF. Clinical trial information: NCT01969838; NCT02101268.