Waste activated sludge production and management plays an important role in wastewater treatment plants (WWTPs), especially from an economic point of view. One possible approach is the anaerobic co-digestion of waste activated sludge with others organic substrates in mesophilic and thermophilic conditions in order to exploit the spare volume of existing reactors, recover energy from biogas production, and obtain a fertilizer as final product. The anaerobic trials were carried out at pilot scale, applying two organic loading rates (2.8 and 4.5 kg chemical oxygen demand (COD)/(m(3)·d)) with a hydraulic retention time of 16 and 21 days. Among agro-wastes, wine lees were chosen because of their continuous availability throughout the year, and their high COD content (up to 200-300 g/l, 70% soluble, on average). The addition of wine lees to activated sludge determined a higher biogas production (best yield was 0.40 Nm(3)/kgCOD(fed)) improving the energetic balance of the sludge line of the WWTP. The characterization of both substrates fed and digester effluents was carried out in terms of heavy metals; comparison with EC proposed limits showed that, due to high content of Cu in wine lees, the loading rate of this agro-waste should be limited to maintain good characteristics of final biosolids.