Laparoscopic cholecystectomy (LC) is the gold-standard for the treatment of gallbladder stone disease. In recent years laparoendoscopic single site surgery (LESS) has gained greater interest and diffusion for the treatment of gallstones and also in bariatric and colonic surgery. However, no randomized controlled trials are present in the literature that confirm the clinical advantages of LESS compared with the classic laparoscopic procedures. For this reason, we present the preliminary results of this randomized prospective study regarding the feasibility and safety of LESS cholecystectomy versus classic laparoscopic technique. Between October 2009 and April 2010, 50 patients were randomly assigned to three-port classic laparoscopic cholecystectomy (n = 25) or LESS procedure (n = 25). Exclusion criteria were: (1) previous abdominal surgery, (2) signs of acute cholecystitis, choledocholithiasis, or acute pancreatitis, (3) ASA grade III or more, (4) lack of written informed consent, and (5) BMI ≥ 30 Kg/m(2).All the patients' details were recorded: age, weight, height, body mass index, operative time, length of hospital stay, patients' pain and wound satisfaction score. Abdominal pain was registered at 6, 12, and 24 h postoperatively. Wound satisfaction score (very unsatisfied = 1, unsatisfied = 2, acceptable = 3, satisfied = 4, very satisfied = 5) was registered for each patient at the seventh postoperative day. No differences were registered between the two groups about gender, age, weight, height, and BMI. Also postoperative hospital stay was similar (P = 0.71). In three patients (1 in group A and 2 in group B) a 5-mm trocar was added. Intraoperative cholangiography was performed in five patients (2 in group A and 3 in group B). Mean operative time was significantly longer in LESS procedures (41.3 ± 12.0 versus 35.6 ± 5.8; P = 0.04). Abdominal postoperative pain was similar in LC and LESS cholecystectomy. Wound satisfaction score showed statistically significant differences between the two groups: in LESS group, patients were more satisfied with the presence of a small umbilical medication (P < 0.05). In this randomized prospective study, we conclude that LESS cholecystectomy is an excellent alternative to traditional three-port cholecystectomy for patients with uncomplicated disease, and no previous abdominal surgery. Although no differences are present about hospital stay and postoperative pain compared with classic laparoscopic cholecystectomy, in our experience LESS has had a significant impact on patients' wound satisfaction.