The aim of this study consists in the individuation of the most appropriate configuration for the thermophilic anaerobic digestion of Waste Activated Sludge (WAS); to this purpose, the Anaerobic Digestion Model n degrees 1 (ADM1) was adopted. To enhance the energy production, the sludge underwent a thermal pre-treatment. Semi-continuous tests were performed for 281 days, both with raw and pre-treated WAS. The disintegration constant (k_dis) and the maximum acetate uptake rate (km_ac), were calibrated; the latter parameter was increased up to 2.2 KgCOD Kg(-1)COD d(-1) by the pre-treatment. To evaluate the performances of different plant configurations, the specific methane yield and digester productivity were estimated for varying Hydraulic Retention Times (HRTs) and substrate concentrations. The pre-treatment impact on the substrate resulted in the 20% enhancement of the specific methane production for plants run with HRT <10 days; the most proper input concentration consisted in 30 g of Volatile Solids (VS) d(-1). This procedure enabled to estimate the most appropriate HRT range for a) preventing the biomass washout (6/7 days for lower and 8 days for higher input concentration) and b) maximizing the methane and energy production for unit of digester volume (10/12 days). (C) 2017 Elsevier Ltd. All rights reserved.