Total lymphoid irradiation (TLI) has been used to control renal and cardiac allograft rejection. Data evaluating TLI in bronchiolitis obliterans syndrome (BOS), the physiological manifestation of chronic lung allograft rejection, is very limited. We present our single center experience of the safety and efficacy of TLI in controlling progressive BOS in a retrospective study. Over 12 years, 37 lung recipients (16 M:21 F) who had undergone 13 single; 12 bilateral and 12 heart-lung transplants were treated with TLI for progressive BOS. Grades at time TLI given were BOS 1 (n = 7) BOS 2 (n = 14) BOS 3 (n = 16). Twenty-seven (73%) completed >8/10 fractions, 10 (27%) failed to complete TLI. Two died from advanced BOS during treatment, 8 stopped early (range 3-7 fractions) due to marrow suppression (6) or infection (2). In the 27 recipients who completed >8/10 fractions, decline in FEV1 was 122.7 mls/month pre-TLI and 25.1 mls/month post-TLI, p = 0.0004, mean (95% CI) change in rate of decline was 97.5 (48.2-146.7) mls/month. TLI significantly reduces the rate of decline in graft function associated with BOS. TLI is well tolerated and associated with few serious complications and is an appropriate immunosuppressive approach in progressive BOS.