Background: Orthotopic single lung transplantation (LTX) is now an established treatment modality for patients with end-stage emphysema. LTX has been shown to cause unloading of the right ventricle with improvement in right ventricular (RV) structure and function both immediately and up to weeks after surgery, mostly in patients with severe pulmonary hypertension and decreased RV function. Long-term effects of lung transplantation on both RV and left ventricular (LV) anatomy and function, however, are not well known. Methods: Seventeen patients undergoing LTX for end-stage emphysema and preserved RV function underwent serial electron beam computed tomography RV and LV function studies before, 3 months after, 1 year after, and 2 years after transplantation. Right-sided heart catheterization was performed before transplantation and at 1 and 2 years follow-up. Results: RV end systolic volume decreased significantly (-15.5%), and RV ejection fraction increased significantly (+16%) in the first 3 months after LTX. This change was paralleled by a decrease in pulmonary pressure and vascular resistance, indicating a permanent RV unloading. This improvement was maintained up to 2 years after LTX. LV end-diastolic volume (+25%), LV stroke volume (+29%), and LV muscle mass. (+28%) increased significantly in the first 3 months after LTX. This remodeling was maintained during the 2-year follow-up. Conclusions: Significant changes in cardiac anatomy and function occur shortly after LTX, most likely as a consequence of adaptation to a new hemodynamic state in patients with well preserved RV function before LTX. Furthermore, these acute changes persist for at least 2 years after LTX.