Extravasation of total parenteral nutrition (TPN) delivered via central lines is a known potential complication, but significant extravasations of infusate into the pleural space when using peripherally inserted central catheters (PICCs) have not been reported in adults. We report 2 cases ofpleural cavity extravasation ofTPN delivered via a PICC. Measurement of the glucose level of the effusate is a quick way to determine the presence of TPN and should be considered in any patient receiving TPN via any type of central line with a rapidly developing effusion.