Objective:To determine whether colonization with extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-PE) predicts the risk for subsequent infection and impacts carbapenem-consumption and outcome in intensive care unit (ICU) patients.Design:Prospective cohort study.Setting:The 2 ICUs in the University Hospital Basel in Switzerland.Patients:All patients admitted to the 2 ICUs providing mechanical ventilation and an expected ICU stay >48 hours.Methods:Patients were routinely screened for ESBL-PE carriage by rectal swab on admission. Competing risk regression analyses were applied to calculate hazard ratios (HRs) for infection with ESBL-PE and mortality. Length of hospital stay, length of ICU stay, and duration of carbapenem exposure were compared using the Mann-Whitney U test.Results:Among 302 patients, 24 (8.0%) were colonized with ESBL-PE on ICU admission. Infections with ESBL-PE occurred in 4 patients, of whom 3 (75%) were identified as ESBL-PE colonized on admission. ESBL-PE colonization on admission was associated with subsequent ESBL-PE infection (hazard ratio [HR], 25.52; 95% confidence interval [CI], 2.40–271.41; P = .007) and exposure to carbapenems (HR, 2.42; 95% CI, 1.01–5.79; P = .047), whereas duration of carbapenem exposure did not differ in relation to ESBL-PE colonization (median, 7 days [IQR, 3–8 days] vs median, 6 days [IQR 3–9 days]; P = 0.983). Patients colonized with ESBL-PE were not at increased risk for death overall (HR, 1.00; 95% CI, 0.44–2.30; P = .993) or death attributable to infection (HR, 1.20; 95% CI, 0.28–5.11; P = .808).Conclusions:Screening strategies for detection of ESBL-PE colonization on ICU admission may allow the identification of patients at highest risk for ESBL-PE infection and the correct allocation of empiric carbapenem treatment.