Food Drug and Cosmetic Blue No. 1 dye (FD&C Blue No. 1) is commonly added to enteral nutrition formulations in order to facilitate the detection of gastric aspirate in tracheal secretions of critically ill patients. However, reports of systemic blue dye absorption and associated adverse outcomes are emerging. We report two cases of abnormal systemic absorption of FD&C Blue No. 1 in critically ill patients who subsequently died of refractory shock and metabolic acidosis. Risk factors and mechanisms of FD&C Blue No. 1 toxicity are discussed, and alternate approaches to gastric aspiration detection in critically ill patients are considered.