There are no established guidelines regarding anesthesia with a peripheral nerve block (PNB) in the young adult population with von Willebrand disease (vWD) type I. We present a case of a successful PNB outcome in a 20-year-old male patient with vWD type I, osteogenesis imperfecta (OI), and rheumatoid arthritis (RA) who underwent an intramedullary nailing surgery after suffering a left distal femur fracture secondary to a sports injury. Before the procedure, the patient was treated with HUMATE-P® [antihemophilic factor and von Willebrand factor (human)], ALPHANATE®(antihemophilic factor/von Willebrand factor complex), and aminocaproic acid for hematologic control. Left femoral and popliteal nerve blocks were performed for postoperative pain control. The patient was discharged home uneventfully three days after the surgery. In this case, PNB proved to be a safe and effective alternative in the management of a vWD type I young adult patient with comorbidities. Given the lack of established guidelines, a multidisciplinary team should be involved in the pre and perioperative management of these patients due to the risk of delayed bleeding.