Polylactide and polylactide-co-glycolide microspheres containing a lipophilic model drug (vitamin D3) were prepared by spray drying. The purpose of this work is to evaluate the efficacy of spray drying as a method for microsphere preparation. The study was carried out on five different polymers of lactide class: poly-L-lactide 57000 MW, poly-D,L-lactide 209,000 MW, 109,000 MW, 16,000 MW, and polylactide-co-glycolide 22,000 MW. The process conditions were experimentally assessed for each polymer used. The microspheres obtained were characterized for their shape, size and drug content, and the influence of the polymer on microsphere characteristics was evaluated. Results show that polymer type, polymer molecular weight and its concentration in the spraying solution greatly affect microsphere characteristics. In vitro dissolution tests performed with the rotating bottle method resulted in different release profiles depending on type of polymer and on microsphere morphology.