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In this paper, we present a case study on the optimization of the biostabilization process of an Italian mechanical–biological treatment (MBT) plant to account for changes in feed waste composition related to a progressive increase in separate collection of MSW fractions, biowaste in particular. After ten years of operation (2009–2019), a decrease of the stabilization degree of the output material of the plant was detected, with Dynamic Respiration Index (DRI) values above the established limit of 1,000 mgO2/kgVS/h (average values of 4,000 mgO2/kgVS/h determined weekly for eight weeks). The investigations carried out in 2019 on the waste samples feeding the MBT plant showed that paper and plastic materials constitute around 75% of the input waste to the two aerobic bioreactors of the MBT plant, against 55% at the start-up (2009). Furthermore, the airflow rates and the moisture content analyzed weekly for eight weeks in the bioreactors resulted below the optimal values suggested in the literature. To improve the performances of the biostabilization process, a series of modifications were implemented in the plant. The main modification involved the primary mechanical treatment by varying the mesh size of the screens to 50 mm circular holes mesh. Furthermore, the configuration of the aerobic bioreactors was changed by placing the two bioreactors in series (instead of the previous configuration in parallel) and using a screening unit (25 mm) between the two bioreactors instead of at the end of the process. In this way, the residence time of the materials in the aerobic treatment was enhanced from 16 days with the previous configuration to 27 days. Together with an increase of the airflow rates of around 40% and a water supply of approximately 10% in the bioreactors, these modifications allowed to achieve the desired stability of the output waste, with DRI values below 1000 mgO2/kgVS/h. [ABSTRACT FROM AUTHOR]