The purpose of the present work is the evaluation of the biogas yield from red grape pomace (GP) in anaerobic mesophilic regime. Several factors may influence the biogas yield, namely the heterogeneous nature of the available substrates, the presence of poorly degradable matter, the average size of solid substrates and the mass load. The increase of the specific surface area of the particles makes easy the hydrolysis rate, so the bioavailability of substrates, enhancing the degradation efficiency. Also, an increase of the GP mass load by a factor of two may lead to an increase of the biogas production up to three to four-fold. However, high mass loads may also trigger inhibition lowering the chemical oxygen demand (COD) removal, negative effect that is expected to be attenuated by the supplementation of soluble carbon sources. The COD and phenol removal corroborate the high degradation efficiency of the solubilized substrates in the raw GP. A significant percentage of grape pomace is not completely broken down within the experimental period, remaining as a fraction of the residual sludge, which could be used as biofertilizer. For instance, a biogas yielding up to 144 L biogas / kg volatile solids (VS) added was achieved, value much lower than that considering the entire degraded substrate (which ranged from 521 to 719 L biogas/kg VS removed) and the theoretically estimated value (approximately 800 L biogas/kg VS removed). This preliminary evaluation may provide useful information to carry on planning new experiments to improve the methane yield. The efficiency of anaerobic degradation and the energy consumption associated to the milling process should be considered in the definition of a more reliable situation.