Abstract Background: Some benefits of laparoscopic (LC) and minilaparotomy (MC) cholecystectomy may reflect attenuation of the acute phase response. The authors examined components of this response. Methods: Patients were randomized to LC (n = 11) or MC (n = 11). C-reactive protein (CRP), α-1-antitrypsin (AAT), retinol-binding protein (RBP), transferrin, and albumin were measured preoperatively and on postoperative days 1, 2, 4, and 7. Interleukin-1 receptor antagonist (IL-1ra), IL-6, and tumor necrosis factor (TNF-α) were measured more frequently perioperatively. Peak expiratory flow rate, forced expiratory volume in 1 second, and forced vital capacity were measured daily. Results: The IL-6 increase was more persistent and marked in the MC patients from hour 8 to day 7 postoperatively ( P <0.05). Alterations in CRP, AAT, and albumin were similar. Postoperative deficits of respiratory function correlated with the magnitude of acute phase protein alteration. Conclusions: Minimal access surgery induces an acute phase response that is less prominent after a laparoscopic technique.