Vasoplegic syndrome (VS) occurs in 8-10% of patients following cardiac surgery and is associated with increased morbidity and mortality. Nitric oxide and guanylate cyclase play an important role in this response. Methylene blue, an inhibitor of guanylate cyclase, has recently been advocated as an adjunct in the treatment of catecholamine-refractory VS. We experienced a case of VS after aortic arch replacement surgery, presenting severe hypotension refractory to high-dose norepinephrine and vasopressin. Administration of methylene blue 100 mg led to immediate recovery of arterial pressure. We report this case and review the role of methylene blue in the treatment of catecholamine-refractory VS.