Abstract: Objective To compare the success rate and safety of the short-axis (SAX) approach and long- axis (LAX) approach to ultrasound-guided central venous cannulation. Methods Electronic bibliographic databases including PubMed, Cochrane Library, Science Direct, and Web of Science were searched for randomized controlled trials comparing ultrasound-guided central venous cannulation via the LAX and SAX approaches published during the period from January, 2011 to October, 2017. We extracted the data from the eligible studies and assessed the first-attempt success rate, overall puncture success rate and complication rate of the two approaches. The relative risk (RR) with the 95% CI was calculated using a fixed or random effects model. Results Seven randomized controlled trials were included for meta-analysis. The results showed that the first-attempt success rate was significantly higher in the SAX group than in the LAX group (RR=1.27, 95%CI: 1.11-1.46; P=0.0005, I2=49%), but the overall puncture success rate did not differ significantly between the two approaches (RR=1.04, 95%CI: 0.97-1.10; P=0.27, I2=84% ). The incidence of accidental arterial puncture with the SAX approach was significantly lower than that with the LAX approach (RR=1.04; 95%CI: 1.01- 1.08; P=0.01, I2=30%). Conclusion Ultrasound-guided central venous cannulation via the SAX approach, as compared with the LAX approach, can increase first-attempt success rate and reduce the incidence of accidental arterial puncture.