Correct tip location is crucial for a peripherally inserted central catheter (PICC) to maximize the effects of central venous infusion. However, it is difficult to place the tip in a correct location in neonates because of the unreliable estimated length by surface landmark. Therefore, we evaluated the feasibility and safety of an improved intracavitary electrocardiogram (IC-ECG) technique in guiding PICC placement in neonates based on the ratios of P/R wave amplitudes on IC-ECG. The results showed that all of the 32 neonates whose PICCs had been successfully placed and correct tip position verified by chest radiography acquired qualified P wave on IC-ECG. The average ratio of P/R wave amplitude was 0.6 ± 0.1, with a range of 0.4 to 0.8. The 49 neonates who received IC-ECG-guided PICC catheterization showed higher success rates of correct PICC tip position on the first attempt than traditional, predetermined length estimation on surface landmark (93.9% vs 62.5%, χ = 18.01, P < .001). No significant complications occurred in the studied neonates. Based on these findings, IC-ECG-guided tip placement appears to be a promising approach in improving the success rate of tip location when placing a PICC in neonates.