Background: An inhaled formulation of azithromycin (AZ) may be advantageous for the local treatment of pulmonary infections and associated inflammation without causing the systemic side effects observed with oral formulations. Indications for this therapy include chronic obstructive pulmonary disease and cystic fibrosis. Spray dried combination particle formulations of azithromycin are described for use with the excipient enhanced growth (EEG) concept for high efficiency dry powder aerosol delivery. Methods: Solutions for spray drying using a Büchi Nano spray-dryer were prepared containing azithromycin, a hygroscopic excipient (sodium chloride or mannitol), leucine and poloxamer 188 in water. Two formulations were evaluated for their aerosol performance characteristics in a novel dry powder inhaler developed for high efficiency aerosol delivery. Results: EEG DPI formulations prepared using AZ and mannitol as the hygroscopic excipient had a higher emitted dose (89.3±9.2%) than the AZ and sodium chloride formulations (51.0±4.1%). The AZ and sodium chloride formulation had a lower MMAD (1.2±0.1 µm) than the AZ and mannitol formulation (1.6±0.1 µm), although the fine particle fraction less than 5µm was over 85% of the emitted dose for both formulations. Increasing the loaded dose of the AZ and mannitol formulation from 2 mg to 5 mg had no effect on the aerosol MMAD and fine particle fractions although the emitted dose was reduced from 89.9% to 76.9%. Conclusions: Spray dried azithromycin powders were produced with good aerosolization characteristics suitable for the delivery using the EEG DPI.