Objective To investigate the influence of laparoscopic cholecystectomy( LC) versus open cholecystectomy( OC) on postoperative systemic infection and immune response in patients with acute cholecystitis complicated by choleperitonitis. Methods A prospective randomized controlled trial was performed for 45 patients who had a definite diagnosis of acute calculous cholecystitis complicated by choleperitonitis in Shanghai Liqun Hospital from January 2014 to June 2016. According to surgical procedures,the patients were randomized into LC group( 23 patients) and OC group( 22 patients). The length of hospital stay,postoperative complications,and deaths were evaluated in both groups. Blood samples were collected from all patients before surgery and at 1,3,and 6 days after surgery to compare the changes in neutrophil count,serum levels of C- reactive protein( CRP) and interleukin- 6( IL- 6),and erythrocyte sedimentation rate( ESR),as well as the incidence of endotoxemia. The t- test was used for comparison of continuous data between groups,and the chi- square test was used for comparison of categorical data between groups. Results The LC group had a significantly shorter length of hospital stay than the OC group( 5. 4 ± 2. 7 d vs 10. 2 ± 3. 5 d,t =- 5. 46,P < 0. 001). One patient( 4. 3%) in the LC group and 6( 27. 3%) in the OC group experienced peritoneal abscess after surgery,and there was a significant difference in the incidence rate of complications between the two groups( χ2= 4. 77,P = 0. 03). In all patients,the mortality rate was 17. 8%( 8 /45),with 1( 4. 3%) in the LC group and 7( 31. 8%) in the OC group,and there was a significant difference between the two groups( χ2= 5. 16,P = 0. 02). Of all patients in the OC group,4died of peritoneal abscess,1 died of pulmonary embolism,and 1 died of myocardial infarction; of all patients in the LC group,1 died of myocardial infarction. There were no significant differences in inflammatory markers before surgery between the two groups. At 1,3,and 6 days after surgery,the LC group had significantly lower neutrophil count,serum levels of CRP and IL- 6,and ESR( except at 1 day after surgery) than the OC group( all P < 0. 05). Furthermore,the OC group had a significantly higher concentration of endotoxin than the LC group( P < 0. 05),but the level of endotoxin returned to normal at 2 days after surgery in both groups. Conclusion Compared with OC,LC can reduce the probability of endotoxemia,help with the establishment of immunological defense,and reduce the risk of postoperative infection.