Hemophilia A is an inherited bleeding disorder due to a deficiency of coagulation factor VIII (FVIII). Prevention and treatment of bleeding is traditionally through intravenous infusion of a FVIII concentrate. Modifications of recombinant FVIII (rFVIII) with an aim to prolong the half-life have been modest, thought because FVIII is dependent on plasma von Willebrand factor (VWF) for its half-life. Efanesoctocog alfa (ALTUVIIIO), approved by the Federal Drug Administration (FDA) in February 2023, was made independent of endogenous VWF by linking of the FVIII-binding D'D3 domain of VWF to B-domain deleted single chain FVIII. This review will outline the development of efanesoctocog alfa and the pharmacokinetic and safety data from clinical trials, as well as efficacy data from the phase 3 trials. These data formed the basis for the FDA approval. Efanesoctocog alfa is a new type of FVIII replacement with an extended half-life allowing once weekly dosing to achieve hemostasis and FVIII trough levels of 13-15 IU/dL. This provides a highly effective option for treatment and prevention of bleeding in hemophilia A, where FVIII levels are easily measured. It also provides an option for treatment of bleeding and coverage for surgery with few infusions.