The production of microparticles for inhalation has relied on jet-milling while the potential for crystallization of microparticles has remained underexplored until relatively recently. Aqueous antisolvent crystallization of salmeterol xinafoate (SX) from poly(ethylene glycol) (PEG) and other organic (co)solvent systems was compared in order to evaluate factors determining the resultant microparticle properties. SX was crystallized by the addition of water to solutions of SX in PEG 400, PEG 6000, propan-2-ol, acetone and methanol. Crystalline particles were characterized by laser diffraction sizing, scanning electron microscopy and differential scanning calorimetry; PEG-media were characterized by viscometry. Crystallization of SX from PEG 400 produced crystals that exhibited a narrower size distribution than those crystallized from other conventional organic solvents. SX crystallized from PEG 6000 demonstrated a smaller median particle size (D(v,0.5)=0.92+/-0.04 microm) than PEG 400 crystallized SX (D(v,0.5)=4.50+/-0.61 microm). Crystals produced from PEG 400 (Span=2.49+/-0.10) possessed a narrower particle size distribution (PSD) than those produced from PEG 6000 (Span=10.42+/-0.85). SX crystals displayed a plate-like habit with growth limited to two dimensions irrespective of the initial solvent employed. The importance of the rate of generation of SX supersaturation on the PSD was determined using HPLC analysis. DSC showed PEG-crystallized SX to be free from metastable crystal phases in contrast to SX crystallized from propan-2-ol. Crystallization of SX from PEG was shown to follow classical nucleation theory and the crystallization method represents a viable alternative to the use of conventional solvents for the production of microparticles.