Background: Bronchiolitis obliterans syndrome (BOS) is the major limitation to long-term survival following lung transplantation and strategies to reduce its incidence have remained elusive. Macrolides may stabilize lung function in patients with established BOS. Their role, however, in prevention of BOS remains unexamined. Methods: Survival and BOS-free survival of 102 lung allograft recipients (LARs), transplanted at a single center between July 1995 and December 2001 who routinely received clarithromycin, were compared with two different control groups. The first control group consisted of 44 LARs from the same center who were transplanted from January 2002 onwards and did not receive clarithromycin. The second control group consisted of a contemporaneous cohort of 5089 recipients, transplanted between 1995 and 2001, reported to the United Network for Organ Sharing database. Results: When compared with the first control group, BOS-free survival was reduced in LARs receiving clarithromycin. Univariate (hazard ratio [HR] 3.13, p-value=0.004) and multivariate (HR 3.49, p-value=0.04) analyses showed that routine use of clarithromycin was associated with an increased risk of developing BOS. When compared with the second control group, the five-yr survival of clarithromycin group was similar (p-value=0.24). Conclusions: Routine use of clarithromycin does not delay development of BOS or improve survival. © 2011 John Wiley & Sons A/S.