Background: Emicizumab is a subcutaneously administered humanized, bispecific, monoclonal antibody approved for prophylaxis in people with hemophilia A. Methods: HAVEN 5 (NCT03315455) is a randomized, open-label, phase 3 study of individuals aged >= 12 years with severe hemophilia A without factor VIII (FVIII) inhibitors, or hemophilia A of any severity with FVIII inhibitors, across the Asia-Pacific region. Participants were randomly assigned (2:2:1) to receive emicizumab 1.5 mg/kg once weekly (arm A), emicizumab 6 mg/kg every 4 weeks (arm B), or no prophylaxis (arm C). The primary end point was annualized bleeding rate (ABR) for treated bleeds; ABRs were compared between people receiving emicizumab prophylaxis versus those with no prophylaxis. Secondary end points included ABR for treated target joint bleeds. Safety was also evaluated. Results: From April 26, 2018, to January 4, 2019, 70 of 76 screened participants were enrolled and randomized (arm A, n = 29; arm B, n = 27; arm C, n = 14). ABRs (95% confidence interval) for treated bleeds and treated target joint bleeds, respectively, were: arm A, 1.0 (0.53-1.85) and 0.4 (0.18-1.09); arm B, 1.0 (0.50-1.84) and 0.3 (0.12-0.85); arm C, 27.0 (13.29-54.91) and 8.6 (3.15-23.42). The most common adverse event, upper respiratory tract infection, was reported for 14 of 56 (25.0%; emicizumab) and 2 of 14 (14.3%; no prophylaxis) participants. No thrombotic events, thrombotic micro-angiopathies, or deaths were reported. Conclusion: Emicizumab 1.5 mg/kg once weekly and 6 mg/kg every 4 weeks demonstrated bleed control in this study population, was well tolerated, and could improve use of prophylaxis in people with hemophilia A.