Background: Bladder-preserving therapy with a real-time tumor-tracking radiotherapy system (RTRT system) has been used for muscle-invasive bladder cancer (MIBC) since 1998 in our institution. We evaluate long term outcomes of this therapy. Methods: From 1998 to 2016, 38 patients with a T2-T4N0M0 bladder cancer who were clinically inoperable or refused surgery were enrolled. Transurethral tumor resection (TUR) and 40 Gy irradiation to the whole bladder was followed by TUR of the tumor bed (1st Evaluation) and endoscopic implantation of fiducial markers in the bladder wall around the primary tumor. Then, a boost of 25 Gy was made to the primary tumor using RTRT system. Protocol TUR of the tumor bed was performed 6 months later (2nd Evaluation). Patients with adequate renal function (CCR>45ml/min) received concurrent chemoradiotherapy with nedaplatin (cisplatin analog made in Japan, 70mg/m2 intravenously, day1, day22, day50). Results: Median follow-up for surviving patients was 6 yr. 5- and 10-yr OS were 55%, 40%, and 5- and 10-yr PFS were 55% and 39%, respectively. The CR rate at 1st evaluation was 66%, in those patients 5- and 10-yr OS rates were 70% and 61%. Among the patients with non-CR at 1st evaluation, CR rate at 2nd evaluation was 31%. Local recurrence occurred in 13 patients. One of them was performed cystectomy and 9 were performed TUR and/or bladder injection therapy. 11 patients experienced distant recurrence, 2 of those was performed chemotherapy. In univariate analysis, male (OS; HR: 0.33, 95% CI: 0.12-0.92, PFS; HR:0.25, 95% CI: 0.09-0.69) and PS0-1 (OS; HR: 0.26, 95% CI: 0.09-0.79, PFS; HR: 0.29, 95% CI: 0.10-0.85) were significantly associated with good OS and PFS (shown in Table). In multivariate analysis, the both of these covariates were also significantly associated with good OS and PFS (male; OS; HR: 0.31, 95% CI: 0.11-0.88, PFS; HR: 0.21, 95% CI: 0.07-0.62, PS0-1; OS; HR: 0.25, 95% CI: 0.08-0.76, PFS; HR: 0.24, 95%CI: 0.09-0.75). Conclusions: Bladder-preserving therapy is a considerable option in patients medically unfit for or not desiring cystectomy.