To compare the biochemical outcomes reported after radical prostatectomy (RP) versus high dose permanent prostate brachytherapy (HDPPB) using iodine-125 seeds in the treatment of matched high risk prostate cancer (HiPCa). In this retrospective review, 55 HiPCa patients treated between March 2006 and August 2011, who underwent HDPPB using iodine-125 seeds combined with external beam radiation therapy (EBRT) or androgen deprivation therapy (ADT), were compared with 55 HiPCa patients who underwent RP. Patients were matched for age, prostate-specific antigen (PSA), clinical stage, and Gleason scores. The biochemical outcomes after HDPPB and RP were compared via Kaplan-Meier analysis. Of the 110 patients analyzed, the mean ages, PSA, and Gleason biopsy scores were similar between the two cohorts. Among patients who underwent HDPPB, 20 patients (36.4 %) had received adjuvant EBRT. Of this subsample, most patients (98.2 %) had received adjuvant ADT for 3 months. Among patients with RP, 20 patients (36.4 %) had received adjuvant EBRT, whereas 28 patients had received adjuvant ADT. The mean implanted seed numbers were 92.8, the mean D90 was 218.7 Gy, and the mean V100 was 96.1 % after HDPPB. With regard to oncological outcomes, biochemical disease-free survival rates were similar between the two cohorts (82.6 vs. 81.1 %, p = 0.982). Urethrorectal fistula developed in one patient with HDPPB. RP and HDPPB, using iodine-125 seeds with combined treatment modalities, exhibited similar biochemical recurrence-free survival rates among HiPCa patients. Further prospective studies with greater sample sizes and longer follow-up periods are needed to validate these results.