Objective To analyze the effect of different antimicrobial exposure on infection or colonization of carbapenem-resistant Klebsiella pneumoniae (CRKP), explore the effect of different control groups on the results of observational study of antimicrobial exposure as a risk factor. Methods PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI) and other databases were retrieved, studies that met the inclusion criteria published in the past 10 years were searched. Group 1: control group was the study of carbapenem-susceptible Klebsiella pneumoniae (CSKP); group 2: control group was the study of non-infection or colonization. Revman 5.3 software was used for Meta-analysis and sensitivity analysis. Results A total of 40 studies were included, 32 in group 1 and 8 in group 2. Meta-analysis showed that exposure to carbapenems, quinolones, cephalosporins, β-lactam/β-lactamase inhibitors and other antimicrobial agents increased the risk of CRKP infection. Conclusion Antimicrobial exposure increases the risk of microbial resistance, so rational and standardized use of antimicrobial agents should be strengthened. In the observational study of antimicrobial agents as a risk factor for microbial resistance, the selection of control group has a certain impact on study results, which should be carefully selected according to the purpose of study.