Background: Splicing factor 3B subunit 1 (SF3B1) mutations have been shown to confer a unique phenotype in MDS and MDS/MPN overlap syndromes, with ring sideroblasts, thrombocytosis and favorable prognosis. In myelofibrosis (MF) the frequency of SF3B1 mutation is <10% and may play a less important role in disease outcomes (Lasho et. al, Leukemia, 2011). Methods: We retrospectively analyzed all patients (pts) with WHO-defined MF (primary, including pre-fibrotic MF, or progressed from PV or ET) seen at our center from Jan. 2017 through Jul. 2021. We compared disease phenotypes, MPN driver and co-occurring mutations, cytogenetics, dynamic IPSS (DIPSS) score, transfusion requirements, treatment characteristics and survival outcomes between patients with SF3B1-mutated (SF3B1⁺) and -wild type (SF3B1^-) MF. Results: A total of 381 pts were identified, 29 (8%) of whom were SF3B1⁺. There were similar frequencies of JAK2, CALR, MPL mutations and “triple negative” MF in the 2 groups (Table). The median number of SF3B1 mutations was 1 (range, 1-2); K666N being the most common (52%). The 2 groups were similar in regard to their baseline hemoglobin, white blood cell counts, platelets, co-occurring mutations, symptom burden and DIPSS but more SF3B1⁺ pts were PRBC transfusion-dependent at presentation than SF3B1^- pts (38% vs. 15%, p=0.003). At a median follow up of 17.2 months for the entire cohort (range, 0.1- 52.2 mos., 22.6 mos. for SF3B1⁺ and 16.8 mos. for SF3B1^-), 41 pts had died [14% SF3B1⁺ and 10% SF3B1^-, p=0.5] and 7 pts (1 SF3B1⁺ and 6 SF3B1^-) had leukemic transformation. The median estimated OS was 230 months for SF3B1^- vs. not reached for SF3B1⁺ pts (p = 0.6). Conclusions:SF3B1 mutation is an uncommon event in MF and does not substantially affect disease phenotype and outcomes. MF pts with SF3B1 mutation are more likely to be PRBC transfusion dependent.