Background: Catheter-related bloodstream infections (CRBSIs) are associated with significant morbidity and mortality. We aimed to determine the effectiveness of chlorhexidine (CHG) dressings in preventing incident CRBSI in different settings and types of catheters. Methods: We searched PubMed, Cochrane Library, CINAHL, Embase, and ClinicalTrials.gov through March 2019 for studies with the following inclusion criteria: (1) population consisted of patients requiring short or long-term catheters; (2) CHG dressing was used in the intervention group and a nonantimicrobial impregnated dressing was used in the control group; (3) CRBSI was reported as an outcome. Randomized controlled trials (RCTs) and quasi-experimental studies were included. We used a random-effect models to obtain pooled OR estimates. Heterogeneity was evaluated with I 2 test and the Cochran Q statistic. Results: The review included 21 studies (17 RCTs). The use of CHG dressings was associated with a lower incidence of CRBSI (pooled RR, 0.63; 95% CI, 0.53–0.76). There was no evidence of publication bias. In stratified analyses, CHG dressing reduced CRBSI in ICU adult patients (9 studies, pRR, 0.52; 95% CI, 0.38–0.72) and adults with oncohematological disease (3 studies, pRR, 0.53; 95% CI, 0.35–0.81) but not in neonates and pediatric populations (6 studies, pRR, 0.90; 95% CI, 0.57–1.40). When stratified by type of catheter, CHG dressing remained protective against CRBSI in short-term venous catheters (11 studies, pRR, 0.65; 95% CI, 0.48–0.88) but not in long-term catheters (3 studies, pRR, 0.76:; 95% CI, 0.19–3.06). Other subgroup analyses are shown in Table 1. Conclusions: CHG dressings reduce the incidence of CRBSI, particularly in adult ICU patients and adults with an onco-hematological disease. Future studies need to evaluate the benefit of CHG in non-ICU settings, in neonates and pediatric populations, and in long-term catheters.