OBJECTIVES: Myelofibrosis (MF) is a myeloproliferative disorder characterized by progressive scarring of the bone marrow, splenomegaly and debilitating symptoms. Ruxolitinib, a JAK2 inhibitor, demonstrated rapid and sustained reductions of spleen size and control of MF-related symptoms. This analysis aimed to characterize MF patients treated with ruxolitinib in the real-world setting. METHODS:  Data from a Portuguese hospital were collected prospectively (2013-2015) and included MF patients with splenomegaly refractory to cytotoxic agents and/or the presence of constitutional symptoms, under treatment with ruxolitinib. MPN-SAF TSS was used to assess symptoms and QoL. Data were collected at baseline and after 1, 3, 6 and 12 months of treatment. RESULTS: The registry included 15 patients (86.7% male), with a median age of 68 years. At diagnosis, 80% of patients had primary MF, 6.7% post-polycythemia vera MF and 13.3% post-essential thrombocythemia MF. Risk score DIPSS (Dynamic International Prognostic Scoring System) was classified as intermediate-1 in 40% of patients and intermediate-2 in 60%. At baseline, the median spleen size of patients was 15cm (0cm - 30cm). After starting treatment with ruxolitinib, there was an average (median) reduction of 67% (80%) at the first month and 75% (83%) after one year. The most common adverse events were grade 1 and 2, with anemia as the most frequent (92.9%). Half of the patients experienced anemia G3-4 (n=14). There were no records of neutropenia and thrombocytopenia G3-4. Ruxolitinib also provided significant improvement of MF-related symptoms, including pain, fatigue, night sweats and itching. Seven out of eleven patients who completed MPN-SAF TSS experienced an improvement in the overall QoL. CONCLUSIONS:  Ruxolitinib demonstrated to be an effective therapeutic alternative in reducing splenomegaly in MF patients, with a well-tolerated safety profile. Most patients experienced an improvement in symptoms and quality of life.