Objectives To perform a detailed comparison of the in-house hospital costs of patients undergoing radical perineal prostatectomy (RPP) and radical retropubic prostatectomy (RRP) performed with or without bilateral staging lymph node dissection (BPLND) for localized prostate cancer. Methods A retrospective cost review was done of a cohort of 402 consecutive radical prostatectomies performed at our institution during a 21-month period. The procedure was performed as RPP in 279 (69.4%) and RRP in 123 (30.6%) patients, of whom 10.4% and 61.8%, respectively, underwent BPLND under the same anesthesia. The hospital costs were evaluated for each patient using the categories of surgical, nursing, laboratory/transfusion, and pharmacy. Surgical costs were further subdivided into operating room, anesthesia, and recovery room costs. Univariate and multivariate statistical analyses were applied to identify predictors of procedure-related costs. Results The median hospital costs of patients undergoing RPP ($7195, range $5052 to $36,237) were substantially lower than those of patients undergoing RRP ($9757, range $6935 to $27,771; P = 0.001). The median costs for patients undergoing radical prostatectomy without BPLND were significantly lower in the RPP ($7100, range $5052 to $28,604) versus RRP ($9169, range $6935 to $16,705) patients (P = 0.001). The costs for RPP with BPLND ($10,048, range $7529 to $36,237) versus RRP with BPLND ($9973, range $7658 to $27,771) were not significantly different (P = 0.900). Patient age and nerve-preservation status did not significantly influence the procedure-related hospital costs. Conclusions RPP may result in lower in-house costs per patient than RRP in those patients who do not require BPLND. Total hospital costs depend largely on the factors of operating room time, length of stay, and laboratory and transfusion requirements, which may vary among institutions.