INTRODUCTION: Biannual (ie, every 6 months) mass drug administration of azithromycin has reduced childhood mortality in Niger, but its effects on specific respiratory pathogens are not fully elucidated. METHODS: Across 2 years of the Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) study in Niger, we evaluated 1468 nasopharyngeal swabs from children who presented for care with respiratory symptoms. Swabs were tested by quantitative PCR using a customised TaqMan Array Card that included assays for 19 respiratory pathogens. RESULTS: Nasopharyngeal detection of CONCLUSIONS: Biannual administration of azithromycin to communities in Niger was associated with lower prevalence of TRIAL REGISTRATION NUMBER: NCT02048007.