This work presents an analysis on the suitability of mechanical biological treatment of municipal solid waste in South America, based on two previous experimental investigations carried out in two different countries. The first experiment was performed for determining the mass and volume reduction of MSW in the province of Concepción (Chile). The implemented bench-scale process consisted of a manual classification and separation stage, followed by an in-vessel biological degradation process. The second experiment consisted of a full-scale experiment performed in the city of Estrela (Brazil), where the existing municipal waste management facility was adapted to enhance the materials sorting and separation. Expressed in wet weight composition, 85.5% of the material input in the first experiment was separated for biological degradation. After 27 days of processing, 60% of the initial mass was reduced through degradation and water evaporation. The final fraction destined for landfilling equals 59% of the total input mass, corresponding to about 50% of the initial volume. In the second experiment, the fraction destined to landfill reaches 46.6% of the total input waste mass, whilst also significantly reducing the total volume to be disposed. These results, and the possible recovery of material streams suitable for recycling or for preparing solid recovered fuels, are the main advantages of the studied process.