Vasoplegia, a syndrome of noncardiogenic, non-hypovolaemic vasodilatory hypotension is a common complication of cardiac surgery utilising cardiopulmonary bypass. Vasopressor-sparing strategies have been increasingly used in the management of vasoplegia to minimise the untoward ischaemic and arrhythmogenic effects of vasoconstrictors. A recent study found that hydroxocobalamin, a non-vasoconstricting modulator of nitric oxide pathways, provided a clinically meaningful vasopressor-sparing effect in the first 24 h of vasoplegia. We highlight the broad implications of hydroxocobalamin in the management of vasoplegia associated with on-pump cardiac surgery.