In this study the anaerobic co-digestion of wine lees together with waste activated sludge in mesophilic and thermophilic conditions was tested at pilot scale. Three organic loading rates (OLRs 2.8, 3.3 and 4.5 kgCOD/m3d) and hydraulic retention times (HRTs 21, 19 and 16 days) were applied to the reactors, in order to evaluate the best operational conditions for the maximization of the biogas yields. The addition of lee to sludge determined a higher biogas production: the best yield obtained was 0.40 Nm3biogas/kgCODfed. Because of the high presence of soluble chemical oxygen demand (COD) and polyphenols in wine lees, the best results in terms of yields and process stability were obtained when applying the lowest of the three organic loading rates tested together with mesophilic conditions.