Knotting of intravascular catheters has been well described, and all such cases documented in the literature have occurred during catheter insertion. Knot formation has not been reported during the removal of a peripherally inserted central venous line (Epicutaneo-Cava 2 French 24 gauge) in a neonate. The mechanism of knotting in our case is not fully understood. This case emphasizes the value of plain radiography in detecting the presence of a knot in the line, and is being presented to raise the awareness about knot formation if undue resistance is felt during line removal. Early recognition of this rare but serious complication may avoid line fracture and potential fragment embolization.