Objectives: To estimate the incidence and timing of spontaneous closure of atrial septal defects within the oval fossa, to study the modalities for diagnosis, and predict the need for therapeutic intervention. Methods: We reviewed retrospectively the medical records of patients with isolated atrial septal defects within the oval fossa, so-called “secundum defects”, diagnosed between January 1990 and February 2003. Based on the initial echocardiographic evaluation, we divided defects into small ones measuring from 3 to 5 mm, medium ones from 5 to 8 mm, and large ones greater than 8 mm. Results: We identified 121 patients, 50 (41.3%) of whom had failed to thrive, and 14 (11.6%) had congestive heart failure. At a mean of 44.9 ± 22.1 months following diagnosis, with a range from 12 to 102 months, the defects had closed spontaneously in 31 patients (25.6%). Of 22 patients having small defects, spontaneous closure occurred in 18 (82%) at a mean age of 18.9 ± 10.2 months. Of 27 patients with defects of medium size, 12 (44%) either experienced spontaneous closure, or else the defect effectively became a patent oval foramen, at a mean age of 51.2 ± 32.2 months. Only 1 (1.4%) of the 72 patients with a defect larger than 8 mm in size underwent spontaneous closure. The defects increased in size in 8 patients (6.6%). Intervention was necessary in 76 patients (63%) at a mean age of 75.5 ± 15.2 months. Conclusion: The initial size of a defect within the oval fossa at diagnosis is the best predictor of its natural history. Some defects increase in size with growth, irrespective of their initial size.