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The US Food and Drug Administration approval of ruxolitinib for intermediate- and high-risk myelofibrosis (MF) in 2011 changed the therapeutic landscape of the disease. We investigated the first-line treatment choices for MF patients in the pre- and post-ruxolitinib eras and found that the increased use of ruxolitinib has come at the expense of several agents, but has not significantly affected the utilization of hydroxyurea in the first-line setting.Myelofibrosis (MF) is a chronic myeloproliferative neoplasm that presents with a heterogeneous clinical phenotype and prognosis. Before the US Food and Drug Administration approval of ruxolitinib, treatment options were varied and had limited effect. The increased use of ruxolitinib has drastically altered the MF treatment landscape. In this study, we aimed to clarify the clinical situations in which ruxolitinib is being used and analyze its effect on this landscape.We retrospectively assessed treatment choices for MF patients treated at our institution (n = 309). This population was divided into 2 cohorts on the basis of a diagnosis before (cohort BR: n = 174) or after (cohort AR: n = 135) ruxolitinib approval. Cohorts were further stratified for comparison according to presenting clinical factors.Expectedly, the first-line use of ruxolitinib markedly increased after its approval. AR patients were less likely to receive erythropoiesis-stimulating agents (ESAs; P = .0003) and thalidomide (P = .003) than BR patients. In patients with MF-related symptoms and/or splenomegaly, increased use of ruxolitinib was associated with decreased use of first-line ESA (P = .03) or thalidomide (P = .03). In anemic patients, increased use of first-line ruxolitinib was associated with a decreased use of thalidomide (P = .007). In patients with severe leukocytosis, ruxolitinib use did not significantly increase and hydroxyurea was the preferred first-line agent.Overall, the increased use of ruxolitinib appears to have come predominantly at the expense of thalidomide and ESAs, while not having a large effect on the first-line use of hydroxyurea.