Laparoscopic cholecystectomy is considered a minor surgical procedure. In a prospective, randomized study, we compared the metabolic responses to surgery in two groups of patients submitted to open or laparoscopic cholecystectomy. The aim of the study was to verify if the latter caused less metabolic changes. Blood samples were drawn before the operation (basal), 1 h and 2 h after skin incision, and on the first and second postoperative days. The following parameters were studied: cortisol, renin, and leukocytes, including subpopulations. The mean values for age, weight, height, basal neutrophil and lymphocyte counts, basal values of cortisol and renin of patients, and sex distribution of group 1 patients (open, n = 20) matched with those for group 2 (laparoscopic, n = 20), with the exception of age (p < 0.05). No differences were detected between the two groups in terms of cortisol and renin values. However, the neutrophil count 1 h after skin incision was statistically significantly higher with the laparoscopic approach (p < 0.05). The lymphocyte count on the second postoperative day was also statistically significantly higher in group 2 (p < 0.05). We conclude that when a cholecystectomy is performed, the laparoscopic approach has no advantage over the open approach from the standpoint of the metabolic responses we studied. It appears that leukocytes have a more rapid return to normal values after laparoscopic cholecystectomy. Although pneumoperitoneum is known to be responsible for important cardiorespiratory changes, no worse response was found in the laparoscopic group than in the open group.