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Prolonged infusion of beta-lactam antibiotics is broadly recognized as a strategy to optimize antibiotic therapy by achieving a higher percentage of time that concentrations remain above the minimal inhibitory concentration (% fT>MIC), i.e. the pharmacokinetic/pharmacodynamic (PK/PD) index. However, %fT>MIC may not be the PK/PD index of choice for inhibition of resistance emergence and it is therefore unsure what impact prolonged infusion of beta-lactam antibiotics may have on the emergence of resistance.A retrospective cohort study including 205 patients receiving either intermittent (101 patients) or continuous (104 patients) infusion of piperacillin/tazobactam or meropenem was conducted in the ICU of the Ghent University Hospital. Logistic regression analysis was used to develop a prediction model and to determine whether the mode of infusion was a predictor of emergence of antimicrobial resistance.Resistant strains emerged in 24 out of the 205 patients (11.7%). The mode of infusion was no predictor of emergence of antimicrobial resistance. Infection with Pseudomonas aeruginosa was associated with a significantly higher risk for emergence of resistance.In this retrospective cohort study, the emergence of antimicrobial resistance to piperacillin/tazobactam or meropenem was not related to the mode of infusion.The mode of infusion as predictor of resistance was studied in 205 ICU patients.Overall, antibiotic resistance developed in 12% of the patients.More than half of the resistant strains (58%) were P. aeruginosa.Logistic regression did not identify mode of infusion as a predictor of resistance.P. aeruginosa infection was significantly associated with emergence of resistance.