Context: Blood plasma experiences substantial changes in both volume and composition in patients with chronic myeloproliferative neoplasms (MPN) and represents a large reservoir of cytokines and other mediators of inflammation. Higher estimated plasma volume status (ePVS) has recently been shown to correlate with increased thrombotic risk in polycythemia vera patients. Objective: To estimate clinical and prognostic associations of ePVS in patients with myelofibrosis. Design: Retrospective cohort study. Setting: 6 hematology centers. Patients: 238 myelofibrosis patients, 168 with PMF, 34 with post-PV SMF and 36 with post-ET SMF. Interventions: ePVS was calculated using the Strauss derived Duarte formula: (100-hematocrit (%)/hemoglobin (g/dL) and expressed as dl/g. Main outcome measures: Overall survival (OS) and time to thrombosis (TTT). Results: Median ePVS was 5.8 dl/g and it did not significantly differ between PMF and SMF patients. Among other associations, higher ePVS was significantly associated with higher degree of bone-marrow fibrosis, absence of JAK2-mutation, lower white blood cells (WBC), platelets and hemoglobin, presence of circulatory blasts, higher C-reactive protein, higher lactate dehydrogenase, lower albumin and higher Charlson comorbidity index in an overall cohort, as well as with more pronounced splenomegaly and higher Dynamic International Prognostic Scoring System (DIPSS) risk in primary myelofibrosis (PMF) and higher Mysec-PM risk in secondary myelofibrosis (SMF) patients (P<0.05 for all analyses). Higher ePVS (>5.6 dl/g) was associated with shorter overall-survival (OS) in PMF (HR=2.8, P<0.001) and SMF (HR=2.55, P=0.025) and with shorter time-to-thrombosis in PMF (>7 dl/g, HR=4.1, P=0.009) patients. Associations with overall survival diminished in multivariate analyses after adjustments for DIPSS and Mysec-PM, respectively. Association with TTT remained significant independently of JAK2, WBC and chronic kidney disease. Conclusions: Myelofibrosis patients with more advanced disease features and more pronounced inflammation have higher ePVS, indicative of expanded plasma volume. Higher ePVS is associated with impaired survival in PMF and SMF and higher thrombotic risk in PMF patients.