OBJECTIVES: During 2014-2015 several new products for Hemophilia A and B were approved by the FDA, and many others are still in clinical trials. The objective of this study was to review the trends in design of pivotal clinical trials for Hemophilia A and B. METHODS: Systematic review was conducted to identify new and on-going pivotal clinical for Hemophilia A and B. The inclusion criteria were the indication of Hemophilia and study completion date of 2016 or after. The data field extracted were study title, intervention, sponsor, age subgroups, planned enrollment, study type, study design, completion date and outcome measures. RESULTS: Overall, 30 Phase III clinical studies with total planned enrollment of 2823 patients were identified. The median enrollment for the studies was 75 patients. Majority of the studies were for biologics (57%) and remaining were for drugs (43%). For primary outcomes, 12 of the 30 studies measured number of bleeding episodes and development of inhibitors, 3 were area under the curve (AUC) based outcomes. For secondary outcomes, 22 of the 30 studies measured bleeding episodes, 7 were development of inhibitors, 5 were incidence of surgery, 3 were quality of life and 2 were SF-36. Both primary and secondary outcomes show use of several non-traditional measures. Regarding sponsorship, 28 of 30 were sponsored by the industry (8 by Novo Nordisk, 5 by Biogen, 4 by Baxalta, 3 by Bayer, 2 by Octapharma and 1 by CSL Behring). CONCLUSIONS: This review provides an overview of on-going and future Phase III clinical trials for Hemophilia A and B. Study findings might be useful for design and conduct of new studies.