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We systematically searched the literature to investigate the effects of ultrasound guidance on clinical outcomes in pediatric patients undergoing central venous catheterization. BrightcoveDefaultPlayer10.1542/6138655993001PEDS-VA_2018-1719 Video Abstract CONTEXT: Central venous catheterization is routinely required in patients who are critically ill, and it carries an associated morbidity. In pediatric patients, the procedures can be difficult and challenging, predominantly because of their anatomic characteristics. OBJECTIVE: To determine whether ultrasound-guided techniques are associated with a reduced incidence of failures and complications when compared with the anatomic landmark technique. DATA SOURCES: We conducted a systematic search of PubMed and Embase. STUDY SELECTION: We included randomized controlled trials and nonrandomized studies in which researchers compare ultrasound guidance with the anatomic landmark technique in children who underwent central venous catheterization. DATA EXTRACTION: Study characteristics, sample sizes, participant characteristics, settings, descriptions of the ultrasound technique, puncture sites, and outcomes were analyzed. Pooled analyses were performed by using random-effects models. RESULTS: A total of 23 studies (3995 procedures) were included. Meta-analysis revealed that ultrasound guidance significantly reduced the risk of cannulation failure (odds ratio = 0.27; 95% confidence interval: 0.17–0.43), with significant heterogeneity seen among the studies. Ultrasound guidance also significantly reduced the incidence of arterial punctures (odds ratio = 0.34; 95% confidence interval: 0.21–0.55), without significant heterogeneity seen among the studies. Similar results were observed for femoral and internal jugular veins. LIMITATIONS: Potential publication bias for cannulation failure and arterial puncture was detected among the studies. However, no publication bias was observed when analyzing only the subgroup of randomized clinical trials. CONCLUSIONS: Ultrasound-guided techniques are associated with a reduced incidence of failures and inadvertent arterial punctures in pediatric central venous catheterization when compared with the anatomic landmark technique.