Aim: We present three cases of neonatal cardiac tamponade due to umbilical venous catheterization, a rare, but potentially fatal complication., Methods: Timely diagnosis was made by echocardiography, and an urgent pericardiocentesis revealed TPN fluid. Perforation of the cardial wall was proven by contrast X-ray showing contrast diffusing into the pericardial space., Discussion: Most frequently, perforation has a delayed course and results from endothelial injury, caused by the hyperosmolar fluids, leading to transmural necrosis and thrombosis. Subsequently, the fluid diffuses transmurally across the myocardium into the pericardium. As migration of the catheter tip can occur, we suggest that its position should be checked immediately after insertion and twice a week thereafter., Conclusion: Pericardial effusion and cardiac tamponade should be considered in any infant with a central venous line who develops a rapid, unexplained clinical deterioration. Timely diagnosis and drainage has been proven to be life-saving.