The possibility of applying anaerobic digestion (AD) process of the source-selected organic fraction (SS-OF) of municipal solid waste in the south of Tuscany (IT) territory was proposed and evaluated. With respect to a reference scenario, in which the overall amount of SS-OF and garden waste—expected in 2013—is addressed to aerobic composting process, three alternative scenarios were proposed, modeled, and compared by life cycle assessment (LCA). The first one is based on realizing six AD plants upstream of each already existing aerobic plant. The second one is based on realizing only three centralized anaerobic plants. The third alternative is based on co-digestion of a part of the SS-OF with sludge from waste water treatment plants in existing sludge AD plants; the remaining part of SS-OF is processed in devoted AD plants upstream of each already existing aerobic plant. LCA results show that AD application is always favorable with respect to the reference scenario in which organic wastes are aerobically processed. AD allows for net production of thermal and electric energy, generating negative impacts due to avoided emissions and avoided resource consumptions. Among the compared alternatives of AD application, the scenario based on decentralized plants (one anaerobic plant upstream of each existing aerobic plant) resulted to be most favorable, collecting the best value for almost all the considered environmental indicators.