Background: After interstitial prostate iodine-125 brachytherapy (BT), prostate-specific antigen (PSA) evolution in time could predict overall biochemical relapse, but, considering the single patient, it is influenced by the presentation PSA amount and by the prostatic volume. It is also challenging to differentiate a PSA bounce from a biochemical relapse. Purpose: To determine the usefulness of PSA percentage (PP) defined as the rate between PSA presented by a patient at time "t" and the PSA that the same patient had presented at the time of diagnosis (t0) assumed as 100% in predicting biochemical relapse and in differentiating them from PSA Bounces. Methods and Materials: We included 721 patients from Milan S. Raffaele Turro (399) and Lucca Campo di Marte (then S. Luca) Hospital (322). The mean age of patients was 66.5 years (range, 50-79). Mean followup was 150 months (range, 24-180). For each patient, PSA was recorded before and after iodine-125 BT, and PPs were calculated. Cox regression model, relative operating characteristic curves, and Kaplan-Meier regression model were elaborated, and a cutoff of 20% was defined. Results: We observed that PP > 20% is an independent variable highly associated with relapse risk (p < 0.0001) with a sensitivity of 79.7%, a specificity of 82%, and an hazard ratio of 12.1, since the 6 months of followup. A PSA increase above the nadir should be because of bounce (sensitivity and specificity of 81.4%, p < 0.0001) if patient had experienced at 6 months a PP <20%. Conclusions: PP might represent an early and useful tool, predictive of clinical outcome in patients after BT for prostate cancer. © 2017 American Brachytherapy Society.