Gall stone disease is one of the most frequent gastro-intestinal diseases ends up to surgery. Although laparoscopic cholecystectomy is accepted as treatment of choice in many countries worldwide, but its cost beneficiency and effectiveness in developing countries is controversial and is depended to multiple factors. Role of prophylactic antibiotics in prevention of infection is also controversial. In this study, we included 130 patients with cholelithiases with symptomatic acute /chronic cholecystitis or polyps of gall bladder admitted for surgery in Shohada E Tajrish Hospital between 2006 and 2008. They randomly were treated by either open or laparoscopic cholecystectomy. In each group, patients received cefteriaxon as prophylaxis of infection or isotonic sodium chlorides solution as placebo. In all patients, bile samples during surgery were collected and cultured. We compare patients according to demographic features, body weight ASA score, frequency of empyema, hydrops of gall bladder, cholecystitis, gall stones /polyps at time of admission, mean time of surgery and hospital stay, complications of surgery and infection rate. The aim of this study is to compare the role of surgery method and prophylactic antibiotic in reducing the complications (infection, rupture of gall bladder, spillage of bile /gallstone, need for subhepatic drains), and hospital stay period.