Advances in therapies for hemophilia have led to an increased life expectancy for people with hemophilia. Limited data exist on the aging population of people with hemophilia who face additional challenges of age-related comorbidities. Efmoroctocog alfa (a recombinant factor VIII Fc fusion protein [herein referred to as rFVIIIFc]) and eftrenonacog alfa (a recombinant factor IX Fc fusion protein [rFIXFc]) are extended half-life factor replacements for hemophilia A and B, respectively, with demonstrated long-term safety and efficacy. The objective of this post hoc analysis was to describe long-term outcomes in participants 50+ years of age treated with rFVIIIFc or rFIXFc in pivotal Phase 3 trials and their extension studies: A-LONG (NCT01181128; n=21) and ASPIRE (NCT01454739; n=20 [95%]); B-LONG (NCT01027364; n=26) and B-YOND (NCT01425723; n=16 [62%]). Approximately half of participants (48%) with hemophilia A and 62% of participants with hemophilia B had a comorbidity at baseline. More than half of the participants were taking 1+ concomitant medication at baseline, with arthropathy and joint pain reported as the most common indications. Prophylaxis with rFVIIIFc or rFIXFc in individuals 50+ years of age with hemophilia A or B, respectively, resulted in low annualized bleed rates and improvements in joint health. Positive impacts on health-related quality of life were observed in individuals on either rFVIIIFc or rFIXFc prophylaxis. The results for the older subgroups were consistent with the overall study populations, demonstrating that prophylaxis with rFVIIIFc or rFIXFc provides long-term clinical benefits irrespective of age and presence of target joints in patients with severe hemophilia.