The purpose of this study was to examine patterns of use for oral contraceptive and desmopressin acetate nasal spray, both used in managing menorrhagia in adolescents with von Willebrand disease (vWD). Hospital records of adolescents with documented vWD and menorrhagia were reviewed retrospectively. Subjects with vWD type 1 (n = 36) administered either oral contraceptives (OC) or intranasal desmopressin acetate (DDAVP) and followed from 6 months to 4 years were selected for inclusion. Treatment outcomes were examined with respect to effectiveness and safety. Assessing menstrual blood loss using PBAC scores from pretreatment and treatment periods determined effectiveness. Safety was evaluated by monitoring reported adverse events. No significant differences were identified in treatment effectiveness for controlling menorrhagia in vWD adolescents in the OC and intranasal DDAVP group comparisons: 86% versus 77% (P > 0.05), respectively. When combining both treatment groups, the majority of vWD adolescents, 81% (P > 0.05), experienced alleviation of menorrhagia symptoms. Treatment failures were attributed to either the inability of a regimen to control bleeding or to adverse events, including severe headaches and flushing with DDAVP. Safety outcomes were not significantly greater in vWD patients with menorrhagia when OC were compared with intranasal DDAVP. Both medical approaches, OC and DDAVP nasal spray, used in managing menorrhagia in adolescents with documented type I vWD were well tolerated and showed equivalent effectiveness, and no serious adverse events were reported.