Purpose/Objective(s): To define the optimal dose for I-125 prostate implants by correlating post implant CT dosimetry findings with biochemical failure and toxicity. Materials/Methods: Patients with low to intermediate-risk prostate cancer treated with I-125 brachytherapy were analyzed. Between 2003 and 2009, a total of 682 patients were observed from 24 to 100 months (median: 56 months). According to National Comprehensive Cancer Network risk classification, 457 patients with low-risk, 224 patients with intermediaterisk and one patient with high-risk were included. Implant dose was defined as the D90-P (dose delivered to 90% of the prostate from on the 1month postimplant CT-based dose-volume histogram). The D90s ranged from 126 to 233 Gy (median: 185 Gy). Patients were analyzed by dose categories: <140 Gy (n Z 9), 140 to <160 Gy (n Z 75), 160 to <180 Gy (n Z 196), 180 to <200 Gy (n Z 277), and S 200 Gy (n Z 125). The effect of dose on biochemical control using the ASTRO definition was tested with actuarial methods. Genitourinary (GU) and gastrointestinal (GI) toxicity was prospectively assessed using the Common Terminology Criteria for Adverse Events ver.4.0. The effect of dose on GU and GI toxicity S grade 2 was tested with actuarial methods. Results: Freedom from biochemical failure (FFBF) at 5 years was 95% for all patients. FFBF at 5 years was 67% for D90-P doses <140 Gy, 92% for 140 to <160 Gy, 95% for 160 to <180 Gy, 98% for 180 to < 200 Gy, and 99% for S200Gy (p < 0.001). The most significant cut point was seen at a level of 160 Gy (p Z 0.003), secondly at a level of 180 Gy (p Z 0.006). A multivariate analysis using dose, PSA, Gleason score, T-stage, risk groups, neoadjuvant hormone, prostate volume, technique, and prescription found dose to be the most significant factor affecting FFBF. The incidences of late GU toxicities of S grade 2 at 5 years were 3% for the D90-P doses <160 Gy, 7% for 160 to <180 Gy, and 10% for S180 Gy (p Z 0.054). Five-year rates of any grade 3 GU toxicities were 0%, 2%, and 1%, respectively (p Z 0.145). Rates of late GI toxicities of S grade 2 at 5 years were 0%, 1%, and 3%, respectively (p Z 0.143). Conclusions: Improvements in FFBF rates were seen with increasing D90P levels. Adequate I-125 implants should deliver a D90-P of 160 Gy or higher on the basis of postimplant dosimetry on day 30. Greater D90-P doses are associated with a small increase in late GU toxicity S grade 2, and no increase in grade 3 GU toxicity or any late GI toxicity. This shows the feasibility, safety and better treatment results of high D90s, even with greater than 180 Gy. Author Disclosure: A. Yorozu: None. S. Saito: None. K. Toya: None. K. Yoshida: None.