BACKGROUND: The successful use of azithromycin in lung transplant recipients with Bronchiolitis Obliterans Syndrome (BOS) has been described, its mechanisms of action, however, are not known. We report the largest experience of long-term clarithromycin (CLAR) in lung transplant patients with BOS or potential BOS. METHODS: Transplant recipients receiving CLAR for BOS or potential BOS were included (2000-2008). Response to CLAR was defined as an FEV1 increase of >10% at 6 months compared to the FEV1 recorded at initiation of CLAR. RESULTS: 31 patients were included. 12 recipients (39%) responded to CLAR after 6 months, 10/12 recipients responded already after 3 months. Responders showed a mean FEV1 increase of 732 mL (95% CI: 537-938 mL) by 6 months (p<0.001). Overall, patients experienced a FEV1 decline of 181 mL/month prior to CLAR, and a 25 mL/month decline over the 6-months after initiation of CLAR; p=0.015, mean (95% CI) change in rate of decline 155 (32-279). DISCUSSION: We show that long-term CLAR effectively improves lung function in more than one-third of recipients with BOS or potential BOS, comparable to results reported with long-term azithromycin.