A 44-year-old Caucasian female was admitted with a subarachnoid hemorrhage owing to a multilobular tubular anterior communicating artery aneurysm. Eleven days after the original craniotomy, an epidural hematoma was evacuated. The patient was placed on empiric nafcillin antimicrobial coverage (two g every six hours). Within 24 hours, the onset of epistaxis and oozing of blood from the endotracheal tube and craniotomy site was noted. Recurrent subdural and epidural hematomas necessitated a third emergent craniotomy. The development of an acquired qualitative platelet defect was suggested by the findings of a prolonged template bleeding time and markedly abnormal platelet aggregation/ATP release studies despite a normal platelet count. Nafcillin therapy was immediately discontinued. Clinical bleeding resolved. Subsequent bleeding times and platelet aggregation studies confirmed the nafcillin-induced platelet dysfunction.