In this study, industrial and agro-industrial by-products and residues (BRs), animal manures (AMs), and various types of organic wastes (OWs) were analyzed to evaluate their suitability as substitutes for energy crops (ECs) in biogas production. A comparison between the costs of the volume of biogas that can be produced from each substrate was presented with respect to the prices of the substrates in the Italian market. Furthermore, four different feeding mixtures were compared with a mixture of EC and swine manure (Mixture A) used in a full-scale plant in Italy. Swine manure is always included as a basic substrate in the feeding mixtures, because many of the Italian biogas plants are connected to farms. When EC were partially substituted with BR (Mixture B), the cost (0.28 euro Nm(-3)) of the volume of biogas of Mixture A dropped to 0.18 euro Nm(-3). Furthermore, when the organic fraction of municipal solid waste (OFMSW) and olive oil sludge (OS) were used as possible solutions (Mixtures C and D), the costs of the volume of biogas were -0.20 and 0.11euroNm(-3), respectively. The negative price signifies that operators earn money for treating the waste. For the fifth mix (Mixture E) of the OFMSW with a high solid substrate, such as glycerin from biodiesel production, the resulting cost of the volume of biogas produced was -0.09 euro Nm(-3). By comparing these figures, it is evident that the biogas plants at farm level are good candidates for treating organic residues of both municipalities and the agro-industrial sector in a cost-effective way, and in providing territorially diffused electric and thermal power. This may represent a potential development for agrarian economy.