Background: Central venous cannulation (CVC) is integral to pediatric critical care. While the right internal jugular vein (Rt IJV) remains a conventional site, its anatomical challenges in pediatric patients necessitate the exploration of alternatives. This study aimed to compare the efficacy and safety of the supraclavicular approach for left internal jugular vein (Lt IJV) cannulation against the traditional Rt IJV method, emphasizing both clinical outcomes and patient comfort. Materials and methods: A randomized controlled trial (RCT) was conducted at a tertiary care institution over 4 years (January 2019 to December 2022). Among 200 pediatric patients requiring CVC, 100 were randomized to the supraclavicular Lt IJV technique and 100 to the conventional Rt IJV approach. The primary outcome was the success rate of cannulation on the first attempt. Secondary outcomes encompassed mean attempts to success, time to successful cannulation, and complication incidence. Results: The supraclavicular Lt IJV technique demonstrated a higher success rate on the first attempt compared to the conventional Rt IJV method. Additionally, patients undergoing the supraclavicular approach experienced fewer dressing disturbances and reported increased satisfaction, pointing to the method's potential to enhance patient comfort and adherence. Conclusion: The supraclavicular approach for Lt IJV cannulation presents a viable and potentially superior alternative to the traditional Rt IJV method in pediatric patients. Given its advantages in both procedural success and patient satisfaction, this technique holds promise to influence future guidelines and reshape pediatric CVC practices.