Objective. Determine whether daily bathing with chlorhexidine-based soap decreased methicillin-resistant Staphylococcus aureus (MRS A) transmission and intensive care unit (ICU)-acquired S. aureus infection among ICU patients. design. Prospective pre-post-intervention study with control unit. setting. A 1,250-bed tertiary care teaching hospital. patients. Medical and surgical ICU patients. methods. Active surveillance for MRSA colonization was performed in both ICUs. In June 2005, a chlorhexidine bathing protocol was implemented in the surgical ICU. Changes in S. aureus transmission and infection rate before and after implementation were analyzed using time-series methodology. results. The intervention unit had a 20.68% decrease in MRSA acquisition after institution of the bathing protocol (12.64 cases per 1,000 patient-days at risk before the intervention vs 10.03 cases per 1,000 patient-days at risk after the intervention; /3, -2.62 [95% confidence interval (CI), -5.19 to -0.04]; P p.046). There was no significant change in MRSA acquisition in the control ICU during the study period (10.97 cases per 1,000 patient-days at risk before June 2005 vs 11.33 cases per 1,000 patient-days at risk after June 2005; /3, -11.10 [95% CI, -37.40 to 15.19]; P p.40). There was a 20.77% decrease in all S. aureus (including MRSA) acquisition in the intervention ICU from 2002 through 2007 (19.73 cases per 1,000 patient-days at risk before the intervention to 15.63 cases per 1,000 patient-days at risk after the intervention [95% CI, -7.25 to -0.95]; P p.012)]. The incidence of ICU-acquired MRSA infections decreased by 41.37% in the intervention ICU (1.96 infections per 1,000 patient-days at risk before the intervention vs 1.15 infections per 1,000 patient-days at risk after the intervention; P p.001). conclusions. Institution of daily chlorhexidine bathing in an ICU resulted in a decrease in the transmission of S. aureus, including MRSA. These data support the use of routine daily chlorhexidine baths to decrease rates of S. aureus transmission and infection.