Carvedilol is a drug with low oral bioavailability due to its high first-pass metabolism. The purpose of the present study was to prepare a mucoadhesive dry powder inhaler of this drug loaded in poly(ethylene-co-vinyl acetate)(PEVA) nanoparticles for pulmonary delivery. PEVA nanoparticles were prepared by an O/W solvent evaporation method and coated with different concentrations of chitosan as a mucoadhesive polymer. Encapsulation efficiency, particle size, zeta potential, release efficiency, and mucoadhesive properties of the different formulations were evaluated on mucin substrate. The optimized formulation of nanoparticles was spray dried using lactose and mannitol as carrier powders. The flowability of the obtained powders was checked by Carr's Index and Hausner ratio and the in vitro deposition of the aerosolized drug was investigated using a Next Generation Impactor. Increasing in the particle size and zeta potential of nanoparticles confirmed the settling of the chitosan coating layer on the surface of nanoparticles. The in vitro drug release from coated nanoparticles decreased with increasing of chitosan concentration. Mucoadhesive property of chitosan-coated PEVA nanoparticles was higher than noncoated ones. Spray-dried powders had different aerosilization behavior. Mannitol-based formulation was found to have low density, better flow ability, smaller aerodynamic diameter (daer) and higher fine powder fraction. The results of the present study allow concluding that mannitol spray dried, mucoadhesive nanoparticles of PEVA are suitable inhaler powder for pulmonary delivery of carvedilol. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 39694.