This randomized, multicenter, open-label, Phase 3 study is designed to investigate the efficacy, safety, and pharmacokinetics of emicizumab in participants with hemophilia A regardless of factor VIII (FVIII) inhibitor status. Participants who received episodic therapy with FVIII or bypassing agents prior to study entry and experienced at least 5 bleeds over the prior 24 weeks will be randomized in a 2:2:1 ratio to the following regimens: 1) Emicizumab prophylaxis at 3 milligrams per kilogram (mg/kg) every week (QW) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg QW SC; 2) Emicizumab prophylaxis at 3 mg/kg QW SC for 4 weeks, followed by 6 mg/kg every 4 weeks (Q4W) SC; 3) No prophylaxis (control arm).