Background: To evaluate if interruptions of radiotherapy have any effect on outcomes for men with localized prostate cancer (PCa) treated with definitive external beam radiation therapy (EBRT). Methods: We included men with localized PCa treated with definitive 3DCRT or IMRT of escalated dose (≥74 Gy in daily fraction of 2 Gy, or 70.2 Gy in daily fraction of 2.7 Gy) between 1989 and 2013. Men receiving androgen deprivation therapy, or follow up <1 year were excluded. The nontreatment day ratio (NTDR) was defined as the number of nontreatment days divided by the total elapsed days of therapy, to account for the difference in total RT dose and planned RT duration. NTDR was analyzed for each NCCN risk group. Results: A total of 1,796 men including 861 low risk, 821 intermediate risk, and 114 high risk were included, with median follow up of 53.5 m (range 12 to 185.8 m). The median NTDR was 31% (range 23.1%-71.2%), translating to approximately 2 breaks (each break represents a missed treatment that would be made up in the end) for an 8-week RT with 5 treatments per week. The 75th percentile of NTDR was 33.3%, translating to approximately 4 breaks, which was used as the cutoff to compare the outcomes with NTDR ≥33.3% vs <33.3%. There were no significant differences in freedom from biochemical failure (FFBF), distant metastasis (DM), cancer-specific survival(CSS), or overall survival (OS) for men with NTDR ≥33.3% compared to NTDR<33.3% for each risk group (Table). Multivariable analyses including NTDR, age, race, Gleason score, T stage, and PSA were performed using the PHREG procedure. NTDR ≥33.3% was not significantly associated with increased hazard ratio for outcomes in each risk group compared to NTDR <33.3%. Conclusions: Interruptions of RT do not cause significant difference in outcomes in each risk group for men with localized PCa treated with definitive EBRT of escalated dose.