Radiation induced hemorrhagic cystitis (HC) can occur as early as 3 months after radiation or may not become evident for many years. Significant Grade 3-4 HC occurs in 3 – 8% of post pelvic radiation patients despite advances in administration technique and delivery. Historically, severe hemorrhagic cystitis was associated with a 44% mortality rate despite aggressive urinary diversion and cystectomy. Radiation causes chronic fibrosis, endarteritis and progressive tissue hypoxia of the bladder submucosa and muscular tissue with eventual scarring, mucosal sloughing and symptomatic hemorrhagic cystitis. Radiated tissue is rendered hypoxic, hypocellular, and hypovascular to the point that the tissue is no longer able to heal spontaneously resulting in recurrent symptomatic hematuria.