Summary What is Known and Objective Carbapenem‐resistant Enterobacteriaceae (CRE) are virulent gram‐negative bacilli and cause urgent healthcare problems worldwide. One of the main factors leading to the emergence of CRE is antimicrobial consumption. The objective of this study was to assess how closely the rate of antimicrobial consumption and the prevalences of carbapenem‐resistant Escherichia coli (CR‐EC) and carbapenem‐resistant Klebsiella pneumoniae (CR‐KP) are correlated. Methods A retrospective study was performed at a university hospital in Thailand from January 2013 to September 2016. The prevalence of E coli and K pneumoniae was represented as percentages per species per quarter. The antimicrobial consumption rate per quarter was expressed as the defined daily dose (DDD)/1000 patient‐days. Evaluation of the relationships between the rate of antimicrobial consumption and the prevalences of CR‐EC and CR‐KP was conducted via Pearson's or Spearman's correlation analyses. Results and Discussion During the study period, the prevalence of CR‐EC and CR‐KP was less than 6%; however, significantly increasing prevalences were reported for both CR‐EC (r = 0.55, P = 0.03) and CR‐KP (r = 0.87, P < 0.01). There was a significant increasing trend in the consumption of meropenem (r = 0.65, P = 0.01), levofloxacin (r = 0.63, P = 0.01), ceftriaxone (r = 0.55, P = 0.03), ertapenem (r = 0.52, P = 0.05) and the carbapenem group (r = 0.64, P = 0.01). A significant correlation was observed between CR‐KP prevalence and total carbapenem consumption (r = 0.55, P = 0.04). Moreover, levofloxacin consumption had a significant positive relationship with the prevalence of CR‐KP (r = 0.65, P = 0.01). No positive correlation was found with the prevalence of CR‐EC. What is New and Conclusion The rate of consumption of levofloxacin and carbapenems was the important key factor correlated with the rate of emergence of CR‐KP. This is the first report demonstrating the correlation between levofloxacin consumption and CR‐KP prevalence.