OBJECTIVES: To characterise the economic burden of myelofibrosis and associated areas of unmet need. METHODS: A systematic literature review was performed for world-wide cost-effectiveness, cost and resource studies published between January 2004 and September 2014. Databases included MEDLINE, MEDLINE In-process, EconLit, EMBASE and the Cochrane Library, as well as HTA websites. RESULTS: The search identified 261 cost-effectiveness and 231 cost and resource papers. Following two rounds of assessment, two and eight studies, respectively, were included. Bennett et al., 2013, reported a substantial rise in total costs from USD10,523 in the year prior to diagnosis to USD51,654 in the year after diagnosis. A lifetime model developed by El Ouagari et al., 2012, (based on COMFORT-II data) predicted lifetime costs of CAD494,859 and CAD421,755 for ruxolitinib and best available therapy (BAT), respectively. The model calculated high indirect costs due to employment absenteeism for patients taking ruxolitinib (CAD71,848) and BAT (CAD96,458), indicating high burden for patients and society. Bennett et al. reported that costs were 85% greater in patients with previous anaemia treatment, including transfusions. Vekeman et al., 2015, reported that 18% of transfusion-dependant patients received iron chelation therapy, with significantly higher monthly pharmacy costs vs. those without (mean difference: $1,426, p=0.004). El Ouagari et al. predicted lifetime transfusion costs of CAD18,299 for patients taking ruxolitinib and CAD13,456 for those on BAT, suggesting that patients treated with ruxolitinib may experience worsening of anaemia. This is consistent with COMFORT-I data, which showed that transfusion-dependant ruxolitinib patients increased from 25% at baseline to 40% at Weeks 8-12 (Pardanani and Tefferi, 2014; not identified via this search). CONCLUSIONS: Myelofibrosis leads to significant direct costs for health systems and substantial absenteeism costs for patients. Despite the available treatments, patients with disease and treatment emergent cytopenias and transfusion dependency require additional medical management, further augmenting the economic burden.