SUMMARY The purpose of this analysis was to correlate isotope selection with the urinary symptoms of patients who received a combination of external beam radiotherapy (EBRT) and a transperineal interstitial permanent prostate brachytherapy (TIPPB) boost with either a 103palladium (103Pd) or a 125iodine (125I) radioisotope. Postimplant dosimetry was performed to evaluate both urethral dose and implant quality. The American Urologic Association (AUA) scores in both the 125I and 103Pd groups were similar initially. However, at 1, 3, 6, and 12 months of follow-up, the mean AUA scores for the 125I and 103Pd patients were 18 ± 6 vs. 11 ± 9, 17 ± 7 vs. 11 ± 7, 10 ± 3 vs. 9 ± 4, and 14 ± 8 vs. 7 ± 5, respectively (P < 0.01). The only significant difference between the postimplant dose-volume histogram (DVH) of the 125I and 103Pd implants was the minimum dose that 90% of the urethra received (D90). The increased AUA score of the 125I group was weakly correlated (R2 = 0.20) with the D90 dose but that of the 103Pd patients was not (R2 = 0.00). This suggests that the higher AUA score of the 125I patients was not necessarily the result of the higher D90 dose. Thus, patients who received 103Pd experienced less urinary morbidity than those implanted with 125I. We recommend further validating these findings in prospective studies in which the quality of the 125I and 103Pd implants can be evaluated. © 2002 Wiley-Liss, Inc.