Background: Late treatment failure is often considered to be a rare event. We will assess the influence of the timing of biochemical failure (bF) after definitive brachytherapy (BT) or external beam radiotherapy (EBRT) for prostate cancer on its frequency and association with clinical failure (cF). Methods: Patients with prostate cancer treated between 1996 and 2009 with at least 5 years of follow-up (N= 2,293; 1,060 EBRT, 1,233 BT) were studied in the context of an IRB-approved inception cohort study. Those with a bF were reviewed to determine the timing of bF [< 5 years after treatment (bF<5) vs. > 5 years after treatment (bF>5)] and occurrence of cF post-bF. The bF definition used was the nadir + 2.0 ng/mL version. Results: Of the total patient population, 477 (21%) were noted to have bF- 244 (11%) bF<5 vs. 233 (10%) bF>5. The median follow-up after bF for the bF< 5 group is 41 months while in the bF> 5 group it is 22 months. In the BT group, 94 (8%) failed < 5 years and 87 (7%) failed > 5 years. In the EBRT group, 150 (14%) failed < 5 years and 146 (14%) failed > 5 years. The median PSA value (ng/mL) at the time of bF for all patients, EBRT, and BT in the bF<5 group was 3.70, 3.65, and 3.80, respectively (p=not significant). The median PSA value (ng/mL) at the time of bF for all patients, EBRT, and BT in the bF>5 group was 3.01, 3.01, and 3.04, respectively (p=not significant). Overall, 53.3% of patients in the bF<5 group developed cF while 27% of patients in the bF>5 group developed a cF. The actuarial five year rate of cF for the bF <5 group was 50% vs. 38% for the bF>5 group (p= 0.028). The detection of bF and cF was closely linked to PSA testing frequency ( p < 0.0001). Conclusions: The risk of bF does not appear to decrease >5 years post treatment. Late bF (i.e. >5 years after treatment) may still result in eventual cF. While cF is less common after bF > 5 years post definitive therapy, it still affects 27% of those with bF and is strongly associated with PSA testing frequency. The lower rate of cF after 5 years may relate to the shorter follow-up time for this group.