Background: Trimodality bladder sparing therapy has become an accepted treatment for selected patients with muscle-invasive bladder cancer (MIBC). As the presence of hydronephrosis may reduce complete response rate and survival in trimodality therapy, some investigators deem hydronephrosis as a contraindication for bladder sparing. We have developed a tetra-modality bladder sparing therapy (TeMT) consisting of maximal transurethral resection (TUR), induction chemoradiotherapy (CRT), and partial cystectomy (PC) (Koga et al, BJU Int 2012). TeMT which enables surgical consolidation of the original MIBC site, including uretero-vesical anastomosis if necessary, may provide more chance of bladder sparing for patients with hydronephrosis. Methods: In total, 151 patients with cT2-3N0M0 MIBC (median age 69 years, female/male = 33/118, cT2/3 = 100/51) entered tetra-modality bladder-sparing protocol. After maximal TUR and CRT (40 Gy + cisplatin), response was evaluated via cytology, imaging, and tumor-site rebiopsy. Consolidative PC was performed in complete responders, while radical cystectomy was recommended for others. Extension of ipsilateral intrapelvic ureter in pretreatment computed tomography was graded following the Society for Fetal Urology grading system, then patients with grade 2-3 were classified as with hydronephrosis. Response rate to CRT, MIBC recurrence-free survival, and cancer-specific survival (CSS) were compared between patients with or without hydronephrosis. Results: Hydronephrosis was found in 19 patients (14%), and was associated with lower response rate to CRT (42% in hydronephrosis vs 77% in normal, p = 0.03). On an intent-to-treat basis, patients with hydronephrosis (n = 19) had lower 5-yr CSS than those without it (n = 132) (62% vs 85%, p < 0.01). Among the 106 patients who underwent PC as per protocol, patients with (n = 9) and without hydronephrosis (n = 97) had comparable 5-yr MIBC recurrence-free survival (100% vs 97%, p = 0.11) and CSS (100% vs 93%, p = 0.46). Conclusions: Patients with hydronephrosis should not necessarily be excluded from tetra-modality bladder sparing therapy.