Severe hemorrhagic cystitis (HC) may be a life-threatening complication in allogeneic stem cell transplantation (SCT). In order to improve the strategies for prophylaxis and treatment, we retrospectively analyzed data on patients who underwent SCT at our center from 1990 through 2005. Patients with HC were identified through our database and their medical charts were reviewed. Grades 2-5 and 3-5 HC developed in 109/834 patients (13.1%) and 27/834 patients (3.2%), respectively. The frequency of HC decreased over the time from 18.0% in 1990-1992 to 9.5% in 2002-2005 (p = 0.005). HC started on a median of 35 (0-166) days post-transplant and persisted for a median of 23 (2-270) days. Transplant-related mortality was 21% in patients without HC, 15% in those with HC of grade 2, 55% in those with grade 3, and 71% in patients with HC of grades 4-5 (p < 0.001). In multivariate analysis, the risk factors for HC were myeloablative conditioning, busulphan, cytomegalovirus infection, hematological malignancy, and acute graft-versus-host disease (aGVHD). With four risk factors, the risk of HC development was 31%. Risk factors for severe HC of grades 3-5 were aGVHD and bacteremia.