We report the largest single-center experience with extracorporeal photopheresis (ECP) for bronchiolitis obliterans syndrome (BOS) and recurrent acute rejection (AR) after lung transplantation. Lung transplant recipients undergoing ECP for BOS and recurrent AR were included (1997-2007). The rate of forced expiratory volume in 1 second (FEV1) decline was used as the primary measure and graft survival post-ECP as the secondary measure of efficacy. Twenty-four transplant recipients were included (BOS, n=12; recurrent AR, n=12). In recipients with BOS, decline in FEV1 was 112 mL/month before the start of ECP and 12 mL/month after 12 ECP cycles (P=0.011), mean (95% CI) change in rate of decline was 100 (28-171). Median patient survival was 7.0 (range, 3.0-13.6) years, median patient survival post-ECP 4.9 (range, 0.5-8.4) years. No ECP-related complications occurred. Extracorporeal photopheresis reduces the rate of lung function decline in recipients with BOS and is well tolerated. Furthermore, recipients with recurrent AR experience clinical stabilization. However, the underlying mechanism of ECP remains subject to further research.