RATIONALE: Bronchiolitis obliterans syndrome (BOS) is the primary limiting factor for long-term survival following lung transplantation, and has previously been associated with microbial infections. OBJECTIVE: To cross-sectionally and longitudinally characterize microbial communities in allografts from transplant recipients with and without BOS using a culture-independent method based on high-throughput sequencing. METHODS: Allografts were sampled by bronchoalveolar lavage (BAL), and microbial communities were profiled using 16S rRNA gene amplicon pyrosequencing. Community profiles were compared using the weighted Unifrac metric and the relationship between microbial populations, BOS, and other covariates was explored using PERMANOVA and logistic regression. MEASUREMENTS AND MAIN RESULTS: Microbial communities in transplant patients fell into two main groups, those dominated by Pseudomonas or those dominated by Streptococcus and Veillonella which appear to be mutually exclusive lung microbiomes. Aspergillus culture was also negatively correlated with the Pseudomonas-dominated group. The re-establishment of dominant populations present in patients pre-transplant, notably Pseudomonas in CF individuals, was negatively correlated with BOS. CONCLUSIONS: Re-colonization of the allograft by Pseudomonas in CF individuals is not associated with BOS. In general, re-establishment of pre-transplant lung populations in the allograft appears to have a protective effect against BOS, whereas de novo acquisition of microbial populations often belonging to the same genera may increase the risk of BOS.