Background Decellularized porcine small intestine submucosa (CorMatrix, Atlanta, GA) patches have been used in the repair of congenital heart malformations. Tissue reaction to the material may create hemodynamic dysfunction and necessitate explantation. We reviewed our series of congenital cardiac patients who had a reoperation after the implantation of CorMatrix patches. Methods Medical records of pediatric cardiac patient who received CorMatrix patches and those of patients who underwent reoperation were reviewed. Routine histologic sections of explanted CorMatrix specimens were examined. Results Of 25 patients who had received CorMatrix patches during cardiac operations at our institution, 6 patients had undergone reoperations. All patients had hemodynamically significant lesions at the site of the CorMatrix implantation. Explanted specimens were associated with an intense inflammatory reaction consisting of numerous eosinophils, histiocytes, and plasma cells, with accompanying granulation tissue and fibrosis. Conclusions Reaction to implanted CorMatrix patches may cause hemodynamic dysfunction and produce an intense, predominantly eosinophilic inflammatory response with developing fibrosis. Although our report is limited to a small sample of congenital cardiac patients, one should take precautions in its use in pediatric cardiac patients, and long-term follow-up is warranted.