Anaerobic digestion of livestock wastes with carbon rich residues was studied. Swine manure and poultry litter were selected as livestock waste, and vegetable processing waste was selected as the rich carbon source. A Central Composite Design (CCD) and Response Surface Methodology (RSM) were employed in designing experiments and determine individual and interactive effects over methane production and removal of volatile solids. In the case of swine manure co-digestion, an increase in vegetable processing waste resulted in higher volatile solids removal. However, without a proper substrate/biomass ratio, buffer capacity of swine manure was not able to avoid inhibitory effects associated with TVFA accumulation. Regarding co-digestion with poultry litter, substrate concentration determined VS removal achieved, above 80 g VS L(-1), NH(3) inhibition was detected. Statistical analysis allowed us to set initial conditions and parameters to achieve best outputs for real-scale plant operation and/or co-digestion mixtures design. (C) 2010 Elsevier Ltd. All rights reserved.