OBJECTIVE: To report a prospective, controlled, non-randomized patient study to determine the systemic response to extraperitoneal laparoscopic (eLRP) and open retropubic radical prostatectomy (RRP). PATIENTS AND METHODS: In all, 403 patients who had eLRP (163) or open RRP (240) were recruited; patients in both groups had similar preoperative staging. In addition to peri-operative variables (operative duration, complications, blood loss, transfusion rate, hospitalization, catheterization), oncological data (Gleason score, pathological stage, positive margins) were also compared. The extent of the systemic response to surgery-induced tissue trauma was measured in all patients, by assessing the levels of acute-phase markers C-reactive protein (CRP), serum amyloid A (SAA), interleukin-6 (IL-6) and IL-10 before, during and after RP. RESULTS: The duration of surgery, transfusion rate, hospital stay and duration of catheterization were comparable with those in previous studies. There was an increase in IL-6, CRP and SAA but no change in IL-10, and no differences between eLRP and RRP over the entire period assessed. CONCLUSION: The invasiveness of eLRP could not be substantiated objectively based on the variables measured in this study. The surgical trauma and associated invasiveness of both methods were equivalent.