OBJECTIVE Radical retropubic prostatectomy (RRP) is associated with intraoperative blood loss. We studied whether regional hemodilution using intracavernosal saline infusion has an impact on blood loss during RRP. METHODS This is a prospective, randomized controlled study. There were 16 patients treated with intracavernosal saline infusion, and 17 did not receive infusion and served as the control group. Patients who received neoadjuvant therapy and those who underwent pelvic lymph node dissection or salvage RRP were excluded. Both corpora were infused in a pressure of 80-cm water. Clinical, pathologic, and laboratory parameters were evaluated and compared. Intraoperative actual blood loss was calculated. RESULTS Blood loss was significantly higher in the control group (1,036 +/- 176 vs. 482 +/- 184 ml; P < 0.001). Postoperatively, 3 control patients received 2 packed-cell units each. There were no differences between the 2 groups in regard to patient's age, comorbidities, body mass index, American Society of Anesthesiologists score, prostate-specific antigen level, clinical or pathologic stage, Gleason score, prostate specimen weight, and operating time. Localized penile edema developed in 6 patients (37.5%) that resolved spontaneously 48 hours postoperatively. None of the patients had symptoms or signs of systemic fluid overload. CONCLUSIONS Our result indicates that localized hemodilution using intracavernosal saline infusion is feasible, safe, and significantly decreases blood loss during RRP.