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Background A new syndrome of hematuria in horses has been documented. Hypothesis/objectives Hemorrhagic cystitis is a novel cause of stranguria and hematuria in horses. This syndrome may be difficult to differentiate from bladder neoplasia because they share several clinical features. Animals Eleven horses with idiopathic hemorrhagic cystitis and 7 horses with bladder neoplasia. Methods Retrospective cohort study. Results Hemorrhagic cystitis was detected on cystoscopy of affected horses, with hemorrhagic and thickened apical bladder mucosa. Clinical signs and endoscopic appearance of the bladder resolved within 3-8 weeks. Histopathology of bladder mucosal biopsy specimens featured neutrophilic and hemorrhagic cystitis. Histopathology was suggestive of dysplasia or neoplasia in 3 horses with hemorrhagic cystitis, yet the horses experienced complete resolution, suggesting that small biopsy specimens obtained by endoscopy can be difficult to interpret. Horses with bladder neoplasia had lower hematocrits, were older, more likely to be female, and more likely to have a mass detected on ultrasonographic examination of the bladder than horses with hemorrhagic cystitis syndrome. Conclusions and clinical importance Hemorrhagic cystitis represents a novel differential diagnosis for horses with hematuria, and is associated with a favorable prognosis. Although histopathology may suggest a neoplastic process, affected horses should be monitored cystoscopically, because complete resolution of hemorrhagic cystitis occurs. The cause of this disease is unknown, and warrants investigation.