Background/Aims: Laparoscopic cholecystectomy is a so called mini-invasive surgical procedure, and on this basis, we investigated whether and how the immune response is modified in patients after laparoscopic cholecystectomy compared to patients who under-went open cholecystectomy. Methodology: In a prospective, nonrandomized trial, 35 patients underwent laparoscopic cholecystectomy and 31 open cholecystectomy. Immune activity (neutrophils, total lymphocytes, lymphocyte subpopulations, human leukocyte antigen (HLA-DR), interleukin 6, skin Multitest) was evaluated before surgery and respectively 1, 3, and 6 days postoperatively. Results: One day after surgery, an increase in interleukin 6 (P < 0.01) was noted in patients who had undergone open cholecystectomy, while this para meter was almost unchanged in patients with laparoscopic cholecystectomy. Moreover, skin tests showed a hypo or anergic response in the majority (81.8%) of open cholecystectomy patients compared to laparoscopic cholecystectomy patients (10.5%), (P < 0.01). Finally, monocyte antigen HLA-DR was also reduced in open cholecystectomy patients (P < 0.05). In this group, we noted 2 cases (6.45%) of respiratory tract infection. Conclusions: Even though laparoscopic cholecystectomy requires a longer surgery, it reduces postoperative pain, and hospitalization. It also facilitates rapid recovery, a return to normal activity, avoids postoperative immunosuppression and shows a better postoperative morbidity compared to open surgery.