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Currently, ultrasound-guided central venous catheter (CVC) insertion is recommended in pediatric patients. However, the clinical practice may vary. The primary aim of this study was the overall success rate and the first attempt success rate in ultrasound-guided CVC insertion versus anatomic-based CVC insertion in pediatric patients. The secondary aim was the incidence of associated complications and the procedural time. The physician could freely choose the cannulation method and venous approach. Data were collected for 10 months. Overall, 179 patients were assessed for eligibility and 107 patients were included. In almost half of the patients (48.6%), the percutaneous puncture was performed by real-time ultrasound navigation. In 51.4% of the patients, the puncture was performed by the landmark method. The overall success rate was 100% (n = 52) in the real-time ultrasound navigation group, 96.4% (n = 53) in the landmark insertion group, (p = 0.496). The first percutaneous puncture success rate was 57.7% (n = 30) in the real-time ultrasound navigation group and 45.5% (n = 25) in the landmark insertion group, (p = 0.460). The data show a higher overall success rate and the first success rate in the US-guided CVC insertion group, but the difference was not statistically significant.