Scheduled rotation of treatment of gram-negative antimicrobial agents has been associated with reduction of serious gram-negative infections. The impact of this practice on other nosocomial infections has not been assessed. The purpose of this study was to determine if scheduled antimicrobial rotation reduced rates of acquisition of enteric vancomycin-resistant enterococci (VRE) among 740 patients admitted to an intensive care unit (ICU). The preferred gram-negative agent was ceftazidime during rotation 1 and ciprofloxacin during rotation 2. Unadjusted VRE acquisition rates were 8.5 cases per 1000 ICU days and 11.7 cases per 1000 ICU days during rotations 1 and 2, respectively (P<.01). However, scheduled antimicrobial rotation of ceftazidime with ciprofloxacin had no effect on the risk of acquiring VRE in the ICU after adjustment for known risk factors. Independent predictors of acquisition of VRE were enteral feedings, higher colonization pressure, and increased duration of anaerobic therapy. Our findings can confirm no additional beneficial or adverse effect on VRE acquisition among ICU patients as a result of this practice.