This study investigates for the first time, on laboratory scale, the possible application of an innovative enhanced stabilization process based on sequential mesophilic/thermophilic anaerobic digestion of waste-activated sludge, with low-energy sonication pretreatment. The first mesophilic digestion step was conducted at short hydraulic retention time (3-5 days), in order to favor volatile fatty acid production, followed by a longer thermophilic step of 10 days to enhance the bioconversion kinetics, assuring a complete pathogen removal. The high volatile solid removals, up to 55%, noticeably higher compared to the performances of a single-stage process carried out in same conditions, can guarantee the stability of the final digestate for land application. The ultrasonic pretreatment influenced significantly the fatty acid formation and composition during the first mesophilic step, improving consequently the thermophilic conversion of these compounds into methane. Methane yield from sonicated sludge digestion reached values up to 0.2 Nm(3)/kgVSfed. Positive energy balances highlighted the possible exploitation of this innovative two-stage digestion in place of conventional single-stage processes.