OBJECTIVE: To describe a successful transition process from subcutaneous treprostinil to intravenous epoprostenol after the failure of treprostinil in a patient with idiopathic pulmonary arterial hypertension and present an algorithm to achieve the conversion without significant adverse reactions. CASE SUMMARY: A 25-year-old white female receiving subcutaneous treprostinil 97 ng/kg/min was admitted to the intensive care unit for transition from subcutaneous treprostinil to a target intravenous epoprostenol dose of 72 ng/kg/min via a staggered interval dose adjustment approach. The patient experienced facial flushing, hot flashes, and headache when dose adjustments of the drugs were made simultaneously; however, when dose adjustments were staggered, the adverse reactions did not occur and larger adjustments could be achieved. DISCUSSION: This case demonstrates a suboptimal therapeutic response to treprostinil for the treatment of idiopathic pulmonary arterial hypertension. The transition of treprostinil to epoprostenol is rare; however, in the event therapy change is needed, dosing information is minimal. A staggered transition dosing regimen that accounts for the pharmacokinetic differences between epoprostenol and treprostinil was successfully used in this case. CONCLUSIONS: The approach in this case demonstrates the success of staggered-interval dose adjustments to minimize supratherapeutic symptoms and coincides with the pharmacokinetic profile of the 2 medications.