Objective To investigate the influencing factors for multidrug-resistant organisms( MDRO) infection in patients with chronic calculous cholecystitis. Methods A retrospective analysis was performed for 654 patients with chronic calculous cholecystitis who underwent cholecystectomy in The Third Affiliated Hospital of Guizhou Medical University from February 2014 to December 2019,and the patients were divided into MDRO infection group with 178 patients and non-MDRO infection group with 476 patients. Related clinical data and medical history were recorded,including age,sex,course of disease,body mass index( BMI),presence or absence of diabetes mellitus/stone incarceration/gallbladder atrophy/bile duct stones/gallbladder polyps/pancreatitis,stone size,attack frequency,number of stones,alanine aminotransferase,duration of antibiotic use,frequency of antibiotic use,combined use of antibiotics,application of cholagogic treatment,blood glucose on admission,glycosylated hemoglobin on admission,aspartate aminotransferase,application of traditional Chinese medicine treatment,and presence or absence of MDRO infection and related strains. The t-test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups; a multivariate logistic regression analysis was used to perform a multivariate analysis. Results The MDRO infection rate was 27. 22% in patients with chronic calculous cholecystitis.There were significant differences between the two groups in course of disease( Z = 3. 503,P < 0. 001),BMI( t = 2. 153,P = 0. 032),diabetes mellitus( χ2= 4. 866,P = 0. 027),stone size( t = 3. 276,P = 0. 001),attack frequency( Z = 2. 574,P = 0. 010),stone incarceration( χ2= 14. 880,P < 0. 001),number of stones( Z = 4. 268,P < 0. 001),gallbladder atrophy( χ2= 14. 855,P < 0. 001),gallbladder polyps( χ2= 14. 234,P < 0. 001),glycosylated hemoglobin on admission( t = 2. 233,P = 0. 026),frequency of antibiotic use( t = 2. 302,P = 0. 022),combined use of antibiotics( Z = 3. 314,P = 0. 001),blood glucose on admission( t = 3. 420,P = 0. 001),duration of antibiotic use( t = 2. 024,P = 0. 044),traditional Chinese medicine treatment( χ2= 7. 529,P = 0. 006),and cholagogic treatment( χ2= 9. 826,P = 0. 002). Incarceration( odds ratio [OR]= 2. 476,95% confidence interval [CI]: 1. 544-3. 972,P < 0. 05),gallbladder atrophy( OR = 3. 548,95% CI: 2. 198-5. 725,P < 0. 05),gallbladder polyps( OR = 3. 198,95% CI: 1. 928-5. 305,P < 0. 05),frequency of antibiotic use( OR = 1. 936,95% CI: 1. 257-2. 981,P < 0. 05),and combined use of antibiotics( OR = 3. 429,95% CI: 2. 049-5. 736,P < 0. 05) were independent risk factors for MDRO infection in patients with chronic calculous cholecystitis,while traditional Chinese medicine treatment( OR = 0. 640,95% CI: 0. 433-0. 945,P < 0. 05) and cholagogic treatment( OR = 0. 548,95% CI: 0. 354-0. 847,P < 0. 05) were independent protective factors against MDRO infection in patients with chronic calculous cholecystitis. Conclusion The risk of MDRO infection in patients with chronic calculous cholecystitis can be reduced by rational use of antibiotics,auxiliary cholagogic and traditional Chinese medicine treatment,reduction in combined and repeated use of antibiotics,early surgical treatment in case of indications such as stone incarceration,and avoidance of gallbladder atrophy and polyps caused by long-term recurrent infection.