Influence of air-jet micronization, post-micronization conditioning and storage on the surface properties of budesonide in dry-powder inhaler formulations was investigated. Crystalline budesonide was air jet-micronized and conditioned using organic vapor. Particle engineering was also used to fabricate respirable particles of budesonide. Surface imaging by atomic force microscopy suggested that micronized material possessed process-induced surface disorder, which relaxed upon conditioning with organic vapor. Particle engineered material was devoid of such surface disorder. Surface interfacial properties of all batches were different and correlated to in vitro fine particle delivery. The surface properties and in vitro performance of the conditioned material changed upon storage of the budesonide at 44% relative humidity and 25°C, while the micronized and particle-engineered material remained stable. These data suggest that processing conditions of budesonide affected the surface properties of the material, which was demonstrated to have direct affect on dry-powder inhaler formulation performance.