Objective To evaluate the cardiopulmonary allograft function and to analyze key factors for long-term survival of heart-lung transplantation in a patient survived more than 5 years. Methods On December 17^th, 2003 at Zhongshan Hospital of Fudan University, a homologous heart-lung transplantation was performed on a female who diagnosed with cardiopulmonary failure secondary to congenital atrial septal defect with severe pulmonary hypertension. Heart-lung allograft was preserved with 1 000 mL UW solution and 4 000 mL HTK solution. Postoperative immunosuppressive therapies were managed with Zenapax, cyclosporine A (or tacrolimus), mycophenolate mofetil and corticosteroids. Cyclosporine A maintained with serum trough levels of 100-200 μg/L and tacrolimus with serum trough levels of 8-20 μg/L. Cardiopulmonary allograft functions were evaluated by echocardiogram, pulmonary function test and thoracic CT periodically. Results The patient survived operation and experienced normal daily life with NYHA cardiac function of class Ⅰ-Ⅱ during the follow-up of 5 years and 6 months. Echocardiogram showed left ventricular ejection fraction of 65% to 86%. Pulmonary function test exhibited with nearly normal oxygen exchange, meanwhile, small airway obstruction was detected from one year after operation and keeping stable from then on. Two episodes of severe pneumonia were complicated and treated with antibiotics and fhconazob, no severe acute allograft rejection episode was experienced. Conclusions Heart-lung transplantation proves to be a reliable therapy modality for terminal cardiopulmonary failure. Excellent donor organ preservation, accurate balance of the risk between acute allograft rejection and infection, and strict preventive measures against infection are key factors for long-term survival of heart-lung transplantation.