BACKGROUND: Inhaled nitric oxide (NO) therapy causes selective pulmonary vasodilation in patients with pulmonary hypertension. However, attempts to discontinue inhaled NO may be complicated by abrupt life-threatening rebound pulmonary hypertension (RPH). The purpose of this study was to determine the risk factors to develop RPH and to present the adequate weaning methods. METHODS: We studied 19 consecutive children who were treated with inhaled NO because of pulmonary hypertension after surgery for congenital heart disease. We compared the dose of NO at the time of start and withdrawal, the duration of weaning and treatment, hemodynamic data, and blood gas analysis before inhaled nitric oxide withdrawal, between patients without (group I, n = 13) and with RPH (group II, n = 6). RESULTS: Compared with group I, group II patients were older in age (1204 1688 versus 546 1654 days, P < 0.05), had a lower NO concentration just before withdrawal (3 +/- 1.6 versus 5 +/- 2.6 ppm, P <0.05), a shorter duration of NO weaning period (4 +/- 3.3 versus 15 +/- 13.4 hours, P < 0.05) and received NO therapy for a shorter duration (26 +/- 11.6 versus 57 +/- 46.0 hours, P < 0.05). CONCLUSIONS: We recommend a progressive withdrawal of inhaled nitric oxide to avoid life-threatening RPH observed in the sudden discontinuation.