OBJECTIVES: To better understand the impact of new extended-half-life recombinant factor VIII (rFVIII) treatments relative to conventional rFVIII, we indirectly compared published clinical study results of the factor consumption (FC) and number of injections to treat a bleed during episodic therapy and the FC and annualized bleeding rates (ABR) during prophylaxis with rFVIII Fc fusion protein (rFVIIIFc) and conventional rFVIII. METHODS: A systematic review identified studies of routine prophylaxis in previously treated adults and adolescents with severe haemophilia A for comparison with rFVIIIFc (Mahlangu 2014, Arm 1, individualized prophylaxis). Comparisons were based on the simple differences between studies in median weekly FC, mean prophylaxis ABRs, and the median FC and numbers of injections per bleed. Median weekly FC was reported or estimated from the reported dose and weekly number of injections; FC per bleed was estimated from the reported dose and number of injections per bleed. The number of injections per bleed was calculated from the reported breakdown of bleeds by required number of injections or the total number of injections divided by total bleeds. RESULTS: Four conventional rFVIII studies were included: Tarantino 2004 and Valentino 2012 (Advate®), Recht 2009 (Xyntha®), and Pollmann 2007 (REFACTO®). ABR and weekly FC during prophylaxis were lower with rFVIIIFc compared with each conventional rFVIII study (weighted average mean ABR with rFVIII=5.2 vs. 2.9 with rFVIIIFc; weighted average increase in median weekly FC with rFVIII=24%). The number of injections and FC per bleed were comparable or lower with rFVIIIFc vs. each rFVIII study (weighted average number of injections with rFVIII=1.4 vs. 1.2 with rFVIIIFc; weighted average increase in median FC per bleed with rFVIII=43%). CONCLUSIONS: Based on estimates from published literature, rFVIIIFc requires reduced FC for prophylaxis and bleed resolution compared with conventional rFVIII while maintaining similar or decreased bleeding rates for patients receiving prophylaxis.