The diagnosis of isolated secundum atrial septal defect (ASD) in infancy is uncommon. We studied 26 infants with ASD confirmed at cardiac catheterization. Of these, nine were born prematurely, 15 presented with symptoms of congestive heart failure, and only three were noted to have the clinical features of an ASD in spite of large left to right shunts. All but two patients responded to medical management. Spontaneous closure of the ASD was documented in 39% (ten) of the patients at ages ranging from 2 to 8 years. Twelve patients underwent surgical closure at a mean age of 4 years. No variables at presentation were predictive of subsequent spontaneous closure. In view of the high rate of spontaneous closure and the success of medical therapy, most infants with symptomatic ASD may be managed medically, allowing sufficient time to observe whether spontaneous closure will occur.