Pericardial effusion (PCE) and cardiac tamponade (CT) are rare but life-threatening complications of percutaneouslyinserted central catheter (PICC) use in neonates. There is often a lack in index of suspicion in a neonate with sudden deterioration, resulting in high mortality. We describe a series of three cases of PICC-related PCE/CT in low birth weight infants whose timely diagnosis with echocardiography and pericardiocentesis led to successful resuscitation and survival. We suggest that echocardiographic skills to determine tip position and pericardiocentesis be taught in neonatal resuscitation programs to ensure good outcomes of this otherwise fatal complication.