Gross and microscopic hematuria are well-known complications in patients with sickle cell hemoglobinopathy. Most of these episodes of gross hematuria are self limiting, but rarely may be severe and persistent requiring definitive intervention. Before subjecting these patients to surgical management such as partial or total nephrectomy, several medical therapies of variable benefit have been suggested. We report a patient with sickle cell trait who experienced severe, intractable gross hematuria for 5 months and showed a dramatic response to multiple doses of 1-desamino-8-D-arginine vasopressin (DDAVP) infusion. The remarkable response observed in this patient suggests that treatment with DDAVP infusion may be considered in patients with unremitting gross hematuria associated with sickle cell trait.