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Objective: To evaluate the effectiveness of chlorhexidine (CHG) dressings to prevent catheter-related bloodstream infections (CRBSIs)., Design: Systematic review and meta-analysis., Methods: We searched PubMed, CINAHL, EMBASE, and ClinicalTrials.gov for studies (randomized controlled and quasi-experimental trials) with the following criteria: patients with short- or long-term catheters; CHG dressings were used in the intervention group and nonantimicrobial dressings in the control group; CRBSI was an outcome. Random-effects models were used to obtain pooled risk ratios (pRRs). Heterogeneity was evaluated using the I2 test and the Cochran Q statistic., Results: In total, 20 studies (18 randomized controlled trials; 15,590 catheters) without evidence of publication bias and mainly performed in intensive care units (ICUs) were included. CHG dressings significantly reduced CRBSIs (pRR, 0.71; 95% CI, 0.58-0.87), independent of the CHG dressing type used. Benefits were limited to adults with short-term central venous catheters (CVCs), including onco-hematological patients. For long-term CVCs, CHG dressings decreased exit-site/tunnel infections (pRR, 0.37; 95% CI, 0.22-0.64). Contact dermatitis was associated with CHG dressing use (pRR, 5.16; 95% CI, 2.09-12.70); especially in neonates and pediatric populations in whom severe reactions occurred. Also, 2 studies evaluated and did not find CHG-acquired resistance., Conclusions: CHG dressings prevent CRBSIs in adults with short-term CVCs, including patients with an onco-hematological disease. CHG dressings might reduce exit-site and tunnel infections in long-term CVCs. In neonates and pediatric populations, proof of CHG dressing effectiveness is lacking and there is an increased risk of serious adverse events. Future studies should investigate CHG effectiveness in non-ICU settings and monitor for CHG resistance.