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Background and Importance Following the recent approvals of new JAKinhibitors (fedratinib/momelotinib) for the treatment of Philadelphia-negative chronic myeloproliferative neoplasms (MPN), it is essential to review the real-world experience with the first-in-class agent since its approval more than 10years ago.Aim and Objectives To analyse the clinical characteristics, effectiveness and safety of all patients with MPN treated with ruxolitinib, as well as drug survival.Material and Methods An observational, retrospective and descriptive study was conducted including all patients with MPN treated with ruxolitinib. Demographic, clinical, and disease evolution variables were collected, along with outcome variables (haematocrit for polycythaemia vera (PV), spleen size for all MPN) and safety data. Drug survival was analysed using Kaplan–Meier plots. Statistical analysis was performed with STATA/IC-16.1.Results Thirty-five patients were included (54.3% female; median age at ruxolitinib initiation, 69.8 years [57.1–76.4]): 45.7% PV, 31.4% secondary-myelofibrosis–essential thrombocythaemia, 17.1% primary-myelofibrosis, and 5.7% secondary-myelofibrosis–PV. The most frequent driver-mutation was JAK2 (85.7%). Bone marrow biopsy was performed at diagnosis in 71.4%.The main reasons for starting ruxolitinib were splenomegaly (40.0%), followed by cutaneous toxicity due to hydroxyurea (17.1%), asthenia/constitutional syndrome (17.1%), or resistance to prior therapies (14.3%). At treatment initiation, 54.3% had splenomegaly (mean 5.2±3.7cm). After 8 months of therapy, 84.2% achieved a >50% reduction in spleen size.In PV patients, before ruxolitinib, mean haematocrit was 45.7±3.3%; 68.8% had haematocrit >45% and 56.3% required phlebotomy in the previous 6 months. After 8 months of treatment, 81.3% achieved haematocrit control (haematocrit <45%) and only 12.5% required phlebotomy. Haematocrit remained <45% in 66.7% at 12 months and 75.0% at 24 months.The most frequent adverse events were cytopenias (57.1%), asthenia (25.7%), and herpes-zoster reactivation (11.4%). Dose reduction was required in 54.3% of cases (57.9% due to anaemia). Treatment was discontinued in 28.6% (50.0% due to adverse events).During follow-up, one PV patient progressed to myelofibrosis, seven patients with myelofibrosis progressed to acute-myeloid-leukaemia, and 11 (31.4%) died. Mean drug survival was 7.6years (95% CI 3.1–NR).Conclusion and Relevance In real-world clinical practice, ruxolitinib demonstrates sustained effectiveness in reducing splenomegaly and controlling haematocrit in MPN, with a manageable safety profile. The frequency of dose adjustments and cytopenias highlights the importance of close monitoring and individualised management. Despite its toxicity profile, in our experience, drug survival was higher than that reported in the literature (Palandri et al.).Conflict of Interest No conflict of interest