It is well known that surgery significantly decreases immune responses. Laparoscopic cholecystectomy (LC) is a "miniinvasive" surgical procedure; and on the basis of this consideration we have investigated if and how the immune response is modified in patients after laparoscopic cholecystectomy compared to patients who underwent open cholecystectomy. Immune activity [neutrophils, total lymphocytes count, lymphocytes subpopulations, human leukocyte antigen-DR (HLA-DR)] was evaluated in 53 patients 1 day before surgery and respectively, 1, 3, and 6 days after surgery; 26 patients underwent "open" cholecystectomy and 27 LC. A day after surgery, patients with open cholecystectomy showed a significant increase (p < 0.05) in plasma neutrophils, while they were almost unchanged in LC patients. Monocyte antigen HLA-DR was reduced in patients with "open" cholecystectomy. We recorded two cases (7.6%) of respiratory tract infection in the "open" group. In conclusion, LC strongly reduces postoperative (p.o.) pain and hospitalization, and it promotes earlier recovery and return to normal activity, avoiding p.o. immunosuppression, mostly due to conservation of HLA-DR activity, with less p.o. morbidity compared to that seen with open surgery.