Cardiac vasoplegia remains a significant contributor of morbidity and mortality in cardiac surgery patients after cardiopulmonary bypass. Effective therapeutic options for vasopressor-refractory vasoplegia are limited. We report 3 patients in whom we administered high-dose intravenous ascorbic acid (vitamin C), a cofactor for endogenous catecholamine synthesis, to treat vasoplegia refractory to epinephrine, vasopressin, and norepinephrine after surgery requiring cardiopulmonary bypass. Reductions in vasopressor requirements were observed in all 3 patients, and, in 2 patients, norepinephrine was completely discontinued within 24 hours. Ascorbic acid is a novel potential therapeutic option for cardiac vasoplegia that warrants rigorous prospective studies.