The work is aimed at the preparation and characterization of biodegradable microspheres of poly-D,L-lactide-co-glycolide (PLGA), for the controlled release of clonazepam. The solubility characteristics of this drug make it an interesting example to evaluate the performances of the two most widely used microencapsulation techniques, emulsification solvent evaporation and spray-drying. Several biodegradable PLGA copolymers have been evaluated (RG 502H, RG 503H, RG 503, Boerhinger Ingelheim). They differ in terms of molecular weight and physico-chemical characteristics. The microspheres obtained have been characterized for their morphology, physico-chemical properties (DSC) and in vitro dissolution behaviour. Between the two preparation methods, only spray-drying was suitable for the microencapsulation of clonazepam in PLGA microspheres. In vitro dissolution tests highlight that more sustained release of drug is achieved with the higher (molecular weight) polymer.