<jats:sec> <jats:title>OBJECTIVES:</jats:title> <jats:p>The antimicrobial stewardship program (ASP) is an important quality improvement initiative that is recommended in the ICU. However, the shortage of infectious disease physicians in Japan has led to the need for simpler methods for implementing ASPs. We investigated whether antibiotic time-outs (ATOs) during multidisciplinary rounds as part of an ASP can improve patient survival and reduce the number of days of therapy (DOT) with antibiotics.</jats:p> </jats:sec> <jats:sec> <jats:title>DESIGN:</jats:title> <jats:p>Single-center controlled before-and-after study.</jats:p> </jats:sec> <jats:sec> <jats:title>SETTING:</jats:title> <jats:p>Medical/surgical ICU in a tertiary university medical center in Tokyo, Japan.</jats:p> </jats:sec> <jats:sec> <jats:title>PATIENTS:</jats:title> <jats:p>All patients 16 years old or older admitted consecutively in the ICU between October 2016 and March 2020.</jats:p> </jats:sec> <jats:sec> <jats:title>INTERVENTIONS:</jats:title> <jats:p>An intensivist-driven ICU multidisciplinary round was introduced in October 2016, and ATOs with ICU rounds were implemented in June 2018. ATOs were conducted 3, 7, and 14 days after initiation of antibiotics.</jats:p> </jats:sec> <jats:sec> <jats:title>MEASUREMENTS AND MAIN RESULTS:</jats:title> <jats:p>The primary outcome was the subdistribution hazard ratio (SHR) of survival to hospital discharge compared between multidisciplinary rounds (phase 1) and ATO during multidisciplinary rounds (phase 2) using the multivariable Fine-Gray model. The secondary outcomes were the SHR of survival to ICU discharge and the trends in the DOT with IV antibiotics per 1,000 patient-days between October 2016 and March 2020 by using interrupted time-series analysis. The number of patients in phases 1 and 2 was 777 and 796, respectively. The group that underwent ATO during multidisciplinary rounds showed a significant increase in the survival to hospital discharge in comparison with the multidisciplinary round-only group (SHR, 1.13; 95% CI, 1.02–1.25); however, the SHR of survival to ICU discharge showed no significant intergroup difference. The DOT with total IV antibiotics decreased after ATO implementation (change in intercept, –178.26; 95% CI, –317.74 to –38.78; change in slope, –7.00; 95% CI, –15.77 to 1.78).</jats:p> </jats:sec> <jats:sec> <jats:title>CONCLUSIONS:</jats:title> <jats:p>ATOs during multidisciplinary rounds are associated with improved patient survival and reduced DOT.</jats:p> </jats:sec>