Abstract Background High-level antibiotic consumption plays a critical role in the selection and spread of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) in the ICU. Implementation of a stewardship program including a restrictive antibiotic policy was evaluated with respect to ESBL-E acquisition (carriage and infection). Methods We implemented a 2-year, before-and-after intervention study including all consecutive adult patients admitted for > 48 h in the medical-surgical 26-bed ICU of Guadeloupe University Hospital (French West Indies). A conventional strategy period (CSP) including a broad-spectrum antibiotic as initial empirical treatment, followed by de-escalation (period before), was compared to a restrictive strategy period (RSP) limiting broad-spectrum antibiotics and shortening their duration. Antibiotic therapy was delayed and initiated only after microbiological identification, except for septic shock, severe acute respiratory distress syndrome and meningitis (period after). A multivariate Cox proportional hazard regression model adjusted on propensity score values was performed. The main outcome was the median time of being ESBL-E-free in the ICU. Secondary outcome included all-cause ICU mortality. Results The study included 1541 patients: 738 in the CSP and 803 in the RSP. During the RSP, less patients were treated with antibiotics (46.8% vs. 57.9%; p  < 0.01), treatment duration was shorter (5 vs. 6 days; p  < 0.01), and administration of antibiotics targeting anaerobic pathogens significantly decreased (65.3% vs. 33.5%; p  < 0.01) compared to the CSP. The incidence of ICU-acquired ESBL-E was lower (12.1% vs. 19%; p  < 0.01) during the RSP. The median time of being ESBL-E-free was 22 days (95% CI 16-NA) in the RSP and 18 days (95% CI 16–21) in the CSP. After propensity score weighting and adjusted analysis, the median time of being ESBL-E-free was independently associated with the RSP (hazard ratio, 0.746 95% CI 0.575–0.968; p  = 0.02, and hazard ratio 0.751 95% CI 0.578–0.977; p  = 0.03, respectively). All-cause ICU mortality was lower in the RSP than in the CSP (22.5% vs. 28.6%; p  < 0.01). Conclusions Implementation of a program including a restrictive antibiotic strategy is feasible and is associated with less ESBL-E acquisition in the ICU without any worsening of patient outcome.