We aimed to evaluate the efficiency and safety of one-step procedure combined endoscopic retrograde cholangiopancreatography (ERCP) and laparoscopic cholecystectomy (LC) for treatment of patients with cholecysto-choledocholithiasis. A prospective randomized study was performed on 63 consecutive cholecysto-choledocholithiasis patients during 2008 and 2011. The efficiency and safety of one-step procedure was assessed by comparing the two-step LC with ERCP + endoscopic sphincterotomy (EST). Outcomes including intraoperative features, postoperative features (length of stay and postoperative complications) were evaluated. One- or two-step procedure of LC with ERCP + EST was successfully performed in all patients, and common bile duct stones were completely removed. Statistical analyses showed that length of stay and pulmonary infection rate were significantly lower in the test group compared with that in the control group (P < 0.05), whereas no statistical difference in other outcomes was found between the two groups (all P > 0.05). The one-step procedure of LC with ERCP + EST is superior to the two-step procedure for treatment of patients with cholecysto-choledocholithiasis regarding to the reduced hospital stay and inhibited occurrence of pulmonary infections. Compared with two-step procedure, one-step procedure of LC with ERCP + EST may be a superior option for cholecysto-choledocholithiasis patients treatment regarding to hospital stay and pulmonary infections.