Indomethacin is the conventional medical treatment of patent ductus arteriosus (PDA) in preterms, inducing ductal closure in about 70% of the patients. To increase this success rate, it has been recommended to prolong the standard 3-dose course by an additional 3-dose course. Ibuprofen is as effective as indomethacin with less renal side effects. In order to determine if, like indomethacin, the effectiveness of ibuprofen is increased by a second course, we retrospectively looked at the data of 11 newborns (5 male/6 female, mean gestational age 26.9±1.8 weeks, mean birthweight 957±279 grams) who received 3 additional doses of ibuprofen after failure of the initial standard treatment. Standard ibuprofen treatment (10mg/kg, followed by 5 mg/kg twice at 24-hour intervals) was initiated at a mean age of 2.63±2.3 days in patients with symptomatic PDA on echocardiogram. Recurrence of a hemodynamically significant PDA warranted retreatment by 3 additional doses (same dose regimen). Five patients (nonresponders) still had a wide patent ductus at the end of the first course and received the second course immediately. The remaining six patients (responders) had either a closed or constricted PDA at the end of the first course but had to be retreated 10.4±5.7 (5–19) days later because of secondary relapse. Two patients had mild and transient renal failure during the first course, one of which experienced severe and prolonged renal failure after the second course. Eventually, 7/11 infants (4/5 nonresponders and 3/6 responders) required surgical ligation at a mean age of 22±10 days. In conclusion, when standard ibuprofen therapy fails to induce permanent ductus closure, a second course may avoid surgery in about one third of the patients. However, if standard ibuprofen therapy fails to initiate ductal constriction, the chances of success of a second course seem rather scarce and surgery may be more appropriate.