To present mature results of high-dose-rate brachytherapy (HDR-BT) as monotherapy for intermediate- and high-risk prostate cancer. From 1995 through 2012, 190 patients, 79 with intermediate-risk and 111 with high-risk prostate cancer, were treated with HDR-BT alone using 48 Gy/8 fractions, 54 Gy/9 fractions, or 45.5 Gy/7 fractions over 4 to 5 days. Neoadjuvant with or without adjuvant androgen deprivation therapy was administered to 139 patients, 35 intermediate- and 104 high-risk. Median follow-up time was 92 months (range, 10-227 months), with a minimum of 2 years for surviving patients. Respective rates of cause-specific survival, overall survival, metastasis-free survival, and biochemical no evidence of disease for the intermediate-risk patients were 100%, 100%, 96%, and 93% at 5 years, and 100%, 96%, 91%, and 91% at 8 years. Corresponding rates for the high-risk patients were 97%, 93%, 84%, and 81% at 5 years, and 93%, 81%, 74%, and 77% at 8 years. The cumulative incidence of late grade 2 to 3 genitourinary toxicity was 5% at 5 years and 10% at 8 years, and that of late grade 3 was 0 at 5 years and 1% at 8 years. The cumulative incidence of late grade 2-3 gastrointestinal toxicity was 4% at 5 years and 6% at 8 years, and that of late grade 3 was 0 at 5 years and 2% at 8 years. No grade 4 or 5 toxicity was detected. Our single-institution study with a median 8-year follow-up showed that HDR-BT as monotherapy was safe and effective for patients with intermediate- and high-risk prostate cancer.