Background: The study investigated the success rate of the great saphenous venous catheter placement performed by ultrasound-assisted technique compared with the anatomical landmark approach in infants and toddlers with congenital heart disease and aimed to assess the efficiency and feasibility of this ultrasound-assisted method within the scope of pediatric peripheral intravenous access.Methods: We selected infants and toddlers who underwent congenital cardiac surgery in our medical center from June 1, 2020, to September 7, 2020, by convenience sampling. Children were stratified by the presence of the manifesting cardiac types (cyanotic or acyanotic heart disease). They were assigned to the traditional anatomical landmark group and the ultrasound-assisted group through randomly blocked randomization. The primary outcome was the success rate of the first attempt. The second outcomes included the time to cannulation at the first attempt, the redirections of the first attempt, overall puncture time, and overall redirections of efforts. Besides, a binary logistic regression model was implemented to identify the possible variables related to the success rate of the first attempt.Results: A total of 144 children in our medical center were recruited in the study. The success rate of the first attempt in the ultrasound-assisted group was higher than that of the traditional anatomic landmark group in the stratification of cyanotic children(66.7% vs. 33.3%, P=0.035). Among children of acyanotic kind, the difference in the success rate of the first attempt between the two groups was not significant(57.6% vs. 42.4%, P= 0.194). Overall puncture time (45.5 s vs. 94 s, P= 0.00)and the time to cannulation at the first attempt (41.0 s vs. 60 s, P= 0.00)in the ultrasound-assisted group was less than the traditional landmark group. The ultrasound-assisted group also required fewer redirections of the first attempt (three attempts vs. seven attempts, P=0.002) and fewer total redirections of efforts (two attempts vs. three attempts, P=0.027) than the traditional landmark group. The result of binary Logistic regression showed that the success rate of the first attempt was related to age(OR:1.141; 95% CI=1.010-1.290, P=0.034), the redirections of the first attempt (OR:0.698; 95% CI=0.528 -0.923, P=0.012)and the saphenous venous width(OR:1.181; 95% CI=1.023 -1.364, P=0.023).Conclusions: The ultrasound-assisted technique improves the saphenous venous cannulation sufficiently in children with difficult peripheral veins. The younger age is associated with a higher likelihood of peripheral venous difficulty. The ultrasound-assisted method could effectively screen peripheral veins, such as selecting peripheral veins with a thicker diameter, less puncture discomfort, and a better success rate. This method can be used as a useful and practical way for peripheral venipuncture in children, especially in a difficult situation. It should be widely applied in the operating room. Trial registration: ChiCTR.org.cn(ChiCTR-2000033368). Prospectively registered May 29, 2020.