Pharmacologic modulation to open the KATP channels with diazoxide is useful in treating hyperinsulinemia. Diazoxide is being used more often in neonates with hyperinsulinemic hypoglycemia. This report highlights a case of severe pulmonary hypertension (PH) with re-opening of ductus arteriosus in an extremely premature infant after the use of diazoxide. The rapid onset of PH with respiratory failure was completely reversible. This case emphasizes the need for extreme caution with use of diazoxide in the premature infant population, especially those with chronic lung disease of prematurity. In addition, the use of diazoxide should be limited to the persistent form of congenital hyperinsulinism, after adequate work up has been completed to evaluate for other causes of hypoglycemia. It is postulated that development of PH could be related to KATP agonsim.