The formulation of a new GnRH antagonist (degarelix) in biodegradable poly(DL-lactide-co-glycolide) (PLGA) microparticles was investigated for the development of a 3-month sustained release formulation to treat prostate cancer. The aim was to screen formulation technologies and distinct copolymers to produce microparticles (MP) of different types with good entrapment efficiency (>85%) and peptide purity (>95%) after gamma sterilization. Basically, three types of degarelix-loaded MP (4, 8 and 16% w/w nominal content) were produced with solvent and non-solvent technologies, namely double-emulsion solvent evaporation, spray-drying and two extrusion methods. Besides composition, commercial copolymers differing in residual monomer content and functional group at the carboxylic terminus (acid or ester) were characterized and employed. Peptide loading capacity and purity, as well as shape, size characteristics, and porosity of the produced microparticles were discussed in relation to technology and copolymer choice. Spray-drying and micro-extrusion were the two preferred formulation technologies because of higher entrapment efficiency and better preservation of peptide purity during production and gamma-sterilization. The impact of formulation technologies on the MP characteristics overwhelmed the impact of copolymer selection. Nevertheless, one particular polymer was discarded since it was more susceptible towards radiolytic degradation. The resulting degarelix-MP will be tested in a biological assay for selection of the formulation based on performance.