We report 2 neonatal deaths caused by cardiac tamponade related to peripherally inserted central catheters (PICCs). A total of 3 deaths were noted for 390 PICCs placed, giving an incidence of 0.76%. To determine the magnitude of neonatal death related to PICCs, directors of neonatal intensive care units in the United States were surveyed by means of a questionnaire. Myocardial perforation and pericardial effusion were reported by 29% and 43%, respectively. Deaths were attributed to PICCs by 24% of the respondents. Uniform guidelines need to be formulated to avoid this complication.