Introduction Previous studies reported the efficacy and safety profile of extended half‐life PEGylated recombinant factor VIII (FVIII) rurioctocog alfa pegol (TAK‐660, SHP660, BAX 855) in preventing bleeding in haemophilia A patients. Aim This study evaluated long‐term safety and efficacy of rurioctocog alfa pegol for prophylaxis and treatment of bleeding in previously treated children and adults. Methods In this phase 3b, prospective, open‐label, multicentre study (NCT01945593), eligible patients ≤ 75 years with severe haemophilia A (FVIII < 1%) received prophylactic rurioctocog alfa pegol in a fixed dose (FD, twice‐weekly or less frequent) or pharmacokinetic (PK)‐tailored dose regimen. Co‐primary endpoints were incidence of confirmed FVIII inhibitory antibody development and spontaneous annualized bleed rate (ABR), analysed using a generalised linear model. Secondary endpoints included overall haemostatic efficacy, occurrence of adverse events and health‐related quality of life (HRQoL). Results Overall, 216 patients were included; mean (SD) age at enrolment was 22.8 (15.7) years. No patients developed confirmed FVIII inhibitors. The point estimate (95% CI) of mean spontaneous ABR was 1.20 (0.92‐1.56) among 186 patients receiving twice‐weekly FD prophylaxis and 0.96 (0.54‐1.71) among 25 patients receiving PK‐tailored prophylaxis. Overall haemostatic efficacy was rated good or excellent in 88.6% of all bleeds. No new safety signals were observed. Patients reported improvements in HRQoL measures of pain, and physical and mental well‐being. Conclusion These results highlight the long‐term safety and efficacy of rurioctocog alfa pegol prophylaxis in previously treated children and adults with severe haemophilia A, with a safety profile similar to previous studies and continuing ABR reduction.