BACKGROUND: Primary and secondary myelofibrosis (PMF and SMF) are malignant diseases of hematopoietic stem cell characterized by the neoplastic myeloproliferation and a strong inflammatory milieu. The prognostic nutritional index (PNI) integrates information on albumin and absolute lymphocyte count (ALC) and reflects the inflammatory, nutritional and immune status of a patient. The clinical and prognostic significance of albumin, ALC and PNI in patients with myelofibrosis has not been previously investigated. ----- METHODS: We retrospectively analyzed a cohort of 83 myelofibrosis patients treated in our institution from 2006 to 2017. Albumin, ALC and PNI were assessed in addition to other disease specific markers. ----- RESULTS: The PMF and SMF patients had significantly lower ALC and PNI but similar albumin compared to controls. Lower albumin was significantly associated with older age and parameters reflecting more aggressive disease biology (e.g. anemia, lower platelet levels, higher lactate dehydrogenase (LDH), circulatory blasts, transfusion dependency, blast phase disease), inflammation (higher C reactive protein (CRP), constitutional symptoms) and higher degree of bone marrow fibrosis. Lower ALC was significantly associated with lower white blood cells (WBC) and lower circulatory blasts. Low PNI was associated with lower albumin, lower ALC, anemia, lower WBCs, lower serum iron and lower transferrin saturation. There was no difference in albumin, ALC and PNI regarding the driver mutations. In multivariate analysis adjusted for age and gender, low albumin (hazard ratio [HR] = 4.61, P = 0.001), low ALC (HR = 3.54, P = 0.004) and Dynamic International Prognostic Scoring System (DIPSS) (HR = 2.45, P = 0.001) were able to predict inferior survival independently of each other. Accordingly, low PNI (HR = 4.32, P < 0.001) predicted poor survival independently of DIPSS (HR = 3.31, P < 0.001). ----- CONCLUSION: Assessing albumin, ALC and PNI might improve prognostication in patients with myelofibrosis and could assist in recognition of patients under increased risk of death.