The objectives of this study were to examine the effect of both disease and treatment related prognostic factors on biochemical control and post-treatment biopsy. Two-hundred fifty-eight patients underwent interactive ultrasound guided transperineal prostate implantation for T1-T2 prostate cancer using Iodine-125 (139 patients) and Palladium-103 (119 patients) and were followed from 6-67 months (median, 19). Hormonal therapy with 3 months of leuprolide and flutamide prior to implantation and two months given after the implant was used in 96 patients. Pre-treatment prostate-specific antigen (PSA) had the most significant effect on biochemical failure. Freedom from biochemical failure (FFBF) rates at 4 years were 75% for patients with PSA 1.3-10 ng/ml (144), 74% for patients with PSA 10.1-20 ng/ml (73), and 34% for patients with PSA > 20 ng/ml (41) (P = 0.0004). Gleason score also had a significant effect on FFBF rates. Four-year rates were 81%, 65% and 47% for patients with scores of 2-4 (68), 5-6 (130), and > or = 7 respectively (60) (P = 0.01). These two factors were also significant in multivariate analysis (P = 0.002, 0.007, respectively). Gleason score was the only factor to significantly affect post-treatment biopsy results. Patients with scores of 2-6 had 85% (63/ 74) negative 2-year biopsies versus 62% (13/21) for patients with scores > or = 7 (P = 0.02). Low-risk patients (PSA < or = 10 ng/ml, scores < 7 and stage < T2a) had a 4-year FFBF rate of 88% as compared to 60% for high-risk patients (PSA > 10 ng/ml, score > 6 or stage > or = T2b) (P = 0.02) and had a 95% negative biopsy rate versus 76% for high-risk patients (P = 0.06). Low-risk patients demonstrate high FFBF and negative biopsy rates following implantation. Patients presenting with higher risk prognostic factors such as PSA > 20 ng/ml or Gleason scores > or = 7 may require more aggressive treatment regimens.