The objective of this study was to assess the efficacy of corticosteroids in hastening the recovery of children with postpericardiotomy syndrome, using a randomized double-blind placebo-controlled trial in a tertiary care referral center for pediatric cardiology and cardiac surgery. Twenty-one children, 6 months of age or older (mean age 3.9 years) with postpericardiotomy syndrome following open or closed heart surgery were administered either prednisone 2 mg/kg/day reducing to zero over 14 days (n = 12) or placebo (n = 9). Progress was monitored by daily clinical assessment and alternate day cross-sectional echocardiograms. The primary measures of efficacy were the number of patients in remission at 72 h and at 1 week. No difference in remission rates were found at 72 h, but at 1 week significantly more children treated with prednisone were in remission (placebo 3/9; prednisone 10/12, p = 0.03). A trend to faster resolution of all symptoms and signs was seen in the prednisone-treated group but this was not associated with earlier hospital discharge. Enlargement of pericardial effusion was seen in two children treated with steroids. No complications of treatment were encountered. Prednisone hastens the recovery of children with postopericardiotomy syndrome. Pericardial effusions may increase in size despite the use of corticosteroids.