Purpose: This systematic review and meta-analysis analyzed the effects of 2% chlorhexidine bathing on the incidence of hospital-acquired infection (HAI) and multidrug-resistant organisms (MDRO) in adult intensive care units. Methods: PubMed, CINAHL, Cochrane library, and RISS database were systematically searched, and 12 randomized studies were included in the analysis. Comprehensive Meta-Analysis version 3.0 was used to calculate the effect size using the odds ratio (OR) and a 95% confidence interval (CI). Subgroup analysis was performed according to the specific infection and intervention types. Results: In general, 2% chlorhexidine bathing has a significant effect on the incidence of HAI (OR, 0.59; 95% CI, 0.40~0.86) and MDRO (OR, 0.52; 95% CI, 0.34~0.79). Subgroup analyses show 2% chlorhexidine bathing is effective in bloodstream infections (OR, 0.51; 95% CI, 0.39~0.66) but not for urinary tract infections, ventilator-associated pneumonia infections, and Clostridium difficile infections. Moreover, 2% chlorhexidine bathing alone or its combination with other interventions has a significant effect on the incidence of HAI and MDRO (OR, 0.59; 95% CI, 0.38~0.92). Conclusion: This meta-analysis reveals that 2% chlorhexidine bathing significantly reduces the incidence of HAI and MDRO in intensive care units. The effect of 2% chlorhexidine bathing on pediatric patients or patients at general wards should be further assessed as a cost-effective intervention for infection control.