Abstract Objectives. To compare perioperative costs associated with radical retropubic prostatectomy (RRP) to transperineal brachytherapy (BXRT) with iodine-125 ( 125I) seeds in the treatment of localized prostate cancer. Methods. Actual costs per case for the perioperative period were compiled prospectively for 583 consecutive patients undergoing RRP or BXRT between January 1, 1997 and October 30, 1998 using a hospital-wide cost accounting system. The total cost per case included both technical and professional components. The technical costs included those incurred for anesthesiology, laboratory medicine, medicine, pharmacy, nursing, radiology, 125I seeds, and BXRT technicians. Professional costs included fees from anesthesiology, laboratory, medicine, urology, radiation oncology, and physics. Cases were divided into three groups for analysis: group 1, RRP (n = 404); group 2, BXRT with planning ultrasound performed in the office setting before implantation (n = 107); and group 3, BXRT with planning ultrasound performed in the operating room at the time of implantation (n = 72). Results are reported as relative cost ratios, with RRP assigned a relative cost of 1.0. Results. The total relative perioperative cost for BXRT exceeded that for RRP by 85% to 105%. Technical cost, exclusive of 125I seeds, was substantially lower for BXRT (relative cost 0.36 to 0.42) but was more than offset by the cost of the seeds when comparing total cost with RRP. Performance of the planning ultrasound in the operating room (group 3) increased the total cost by 20%. The categorical technical costs for both BXRT groups were significantly lower for anesthesiology, laboratory medicine, medicine, pharmacy, and nursing but were significantly higher for radiology. The total professional costs were similar for all groups. Conclusions. Perioperative costs of BXRT with 125I seeds are substantially higher than RRP in the treatment of localized prostate cancer, primarily because of the cost of the seeds.