Myelofibrosis (MF) is a rare but aggressive myeloproliferative neoplasm that commonly affects older patients, with a mean age of onset of older than 60 years. At least a third of patients with primary MF are anemic at diagnosis, and nearly all patients become anemic over time; approximately half require red blood cell transfusions within a year of diagnosis. Anemia and transfusion dependence are leading negative prognostic factors for overall survival and are associated with diminished quality of life and increased health care-related economic burden in patients with MF. To describe baseline characteristics, health care resource utilization (HCRU), and costs as a function of transfusion status and anemia severity in patients diagnosed with MF among the US Medicare Fee-For-Service (FFS) population. This retrospective cohort study included patients diagnosed with MF appearing in the 100% Medicare FFS database enrolled between January 1, 2012, and December 31, 2020. Patients were segmented into hemoglobin level cohorts (no, mild, moderate, and severe anemia) and transfusion status cohorts (transfusion independent [TI], transfusion requiring [TR], or transfusion dependent [TD]). Across cohorts, demographics and disease characteristics were assessed at baseline; per patient per month all-cause HCRU and medical and pharmacy costs were reported during follow-up. All results were summarized descriptively. The transfusion status cohort (N = 1,749) included TI (n = 980), TR (n = 559), and TD (n = 210) patients; the anemia severity cohort (N = 365) included patients with no (n = 100), mild (n = 128), moderate (n = 99), and severe (n = 38) anemia. On average, TR and TD patients or those with moderate or severe anemia had numerically higher Deyo-Charlson Comorbidity Index scores than those who were TI or had mild or no anemia. TR and TD cohorts reported numerically greater all-cause outpatient, inpatient, and emergency department utilization vs the TI cohort. All-cause costs were numerically higher in the TD and TR cohorts vs the TI cohort ($14,655 and $14,249 vs $8,191). Incremental increases in HCRU and costs were also observed with increasing anemia severity. All-cause medical and pharmacy costs for no, mild, moderate, and severe anemia cohorts were $4,689, $7,268, $10,439, and $13,590, respectively. This retrospective analysis of the US Medicare FFS database descriptively evaluated patients by transfusion status and anemia severity and showed that costs and HCRU were numerically lower for patients with transfusion independence compared with those with transfusion dependence. Similar trends were seen when comparing patients based on anemia status, with numerically lower HCRU and cost observed with decreasing anemia severity.