Background: Ultrasonic surgery can dissect structures and divide vessels by the effect produced by vibrations in the tissues. It is believed to be less traumatic than the more commonly used monopolar electrosurgery (ELC). Laparoscopic techniques are being used increasingly in surgical conditions complicated by peritonitis. This randomized study compares the acute inflammatory and systemic immune response after laparoscopic cholecystectomy in patients with acute calculous cholecystitis, complicated by peritonitis, performed using either ultrasonic energy or ELC. Patients and Methods: Forty-three patients, scheduled for laparoscopic cholecystectomy, were randomly assigned to treatment using either an ultrasonic device (UC) (n=22 patients) or ELC (n=21 patients). Bacteremia, endotoxemia, white blood cells, the peripheral lymphocyte subpopulation, human leukocyte antigen-DR (HLA-DR), neutrophil-elastase, interleukin-6 and -1, and C-reactive protein (CRP) were investigated. Results: Significantly higher concentration of systemic endotoxin, neutrophil, neutrophil-elastase, interleukin-6 and -1, and CRP were detected intraoperatively and/or postoperatively in the ELC group of patients in comparison with the UC group (P<.05). A statistically significant change in HLA-DR expression was recorded on postoperative Day 1 as a reduction of this antigen expressed on the monocyte surface in patients from the ELC group; no changes were noted in UC patients (P<.05). We recorded 4 patients (22.2%) who developed an intraabdominal abscess in the ELC group and 1 (4%) in the UC group (P<.05). Conclusions: Laparoscopic cholecystectomy after biliary peritonitis, conducted by ELC, increased the incidence of bacteremia and systemic inflammation compared with the UC group. Early enhanced postoperative systemic inflammation may cause lower transient immunologic defense in the ELC group, leading to enhanced sepsis.