C entral venous cannulation (CVC) is commonly used for many well-known indications, with the internal jugular, subclavian, and femoral veins the most common sites for CVC. In some patients, CVC may be extremely complicated, unsafe, or fatal. Use of ultrasound techniques to facilitate CVC may reduce these risks of misplacement and complications. Real-time 2-dimensional ultrasound (RTUS) has become more popular because it can visualize arteries, veins, and surrounding structures by their relative positions. This meta-analysis was undertaken to investigate the effects of RTUS on the clinical outcomes of patients receiving CVC.Several databases were searched for randomized controlled trials (RCTs) that compared outcomes in patients undergoing CVC with either RTUS or the anatomic landmark technique without any ultrasound guidance. Data were extracted from fulltext articles. The principal end points for the analysis were cannulation failure, arterial puncture, hematoma, pneumothorax, and hemothorax.Twenty-five of 1542 potentially relevant articles were included in the analysis. One report had 2 RCTs, giving a total of 26 RCTs with 4185 CVC procedures. Real-time 2-dimensional ultrasound substantially reduced the risk of cannulation failure (relative risk [RR] = 0.18) and reduced the risk of arterial puncture, hematoma, pneumothorax, and hemothorax (RRs = 0.25, 0.30, 0.21, and 0.10, respectively). Heterogeneity was low between studies. Sensitivity analyses indicated that the overall risk estimates for cannulation failure, arterial puncture, and hematoma were not modified by any single study, with RRs ranging from 0.17 to 0.20 for cannulation failure, from 0.22 to 0.28 for arterial puncture, and from 0.24 to 0.35 for hematoma. The superiority of RTUS for risk of cannulation failure was statistically significant in adult patients but not in pediatric patients (RRs = 0.18 and 0.26, respectively). Based on limited data, RTUS was not associated with a reduced risk of arterial puncture, hematoma, pneumothorax, and hemothorax in pediatric patients (RRs = 0.34, 0.13, 0.40, and 0.40, respectively). In addition, high heterogeneity was found in the data for pediatric patients for the risks of cannulation failure and arterial puncture.The pooled results showed that RTUS compared with anatomic landmark led to statistically significant reductions in the incidence of cannulation failure and the risks for accidental arterial puncture, hematoma, pneumothorax, and hemothorax. Because more data in the pediatric population are required, well-designed RCTs for this patient group are needed to clarify the role of RTUS in children.