We analyzed the incidence, complications, and risk factors for late-onset hemorrhagic cystitis (HC) in 256 children undergoing hematopoietic stem cell transplantation (HSCT). Twenty-six recipients (10.2%) developed late-onset HC between 3 and 270 days (median, 33 days) after HSCT. In most patients, the severity of HC was mild to moderate, and spontaneous resolution occurred. Three children developed bladder tamponade, and one required suprapubic cystotomy. Four children died in the early post-transplant period without resolution of HC, but HC was not the direct cause of death in any patient. Twenty-two patients recovered within 6-86 days (median, 16 days) of onset. Three predisposing factors were identified for development of late-onset HC by multivariate analysis: allogeneic HSCT, older age (> or = 7 years), and busulphan for pretransplant conditioning were significantly associated with late-onset HC (P=0.022, P=0.044 and P=0.036, respectively). Excretion of adenovirus type 11 was demonstrated in six of 22 patients at the onset of cystitis. We suspect that reactivation of virus may be a major pathogenic factor in late-onset HC, but several clinical factors are also associated.