The feasibility and cost-effectiveness of hydrogen-based microgrids in facilities, such as public buildings and small- and medium-sized enterprises, provided by photovoltaic (PV) plants and characterized by low electric demand during weekends, were investigated in this paper. Starting from the experience of the microgrid being built at the Renewable Energy Facility of Sardegna Ricerche (Italy), which, among various energy production and storage systems, includes a hydrogen storage system, a modeling of the hydrogen-based microgrid was developed. The model was used to analyze the expected performance of the microgrid considering different load profiles and equipment sizes. Finally, the microgrid cost-effectiveness was evaluated using a preliminary economic analysis. The results demonstrate that an effective design can be achieved with a PV system sized for an annual energy production 20% higher than the annual energy requested by the user and a hydrogen generator size 60% of the PV nominal power size. This configuration leads to a self-sufficiency rate of about 80% and, without public grants, a levelized cost of energy comparable with the cost of electricity in Italy can be achieved with a reduction of at least 25−40% of the current initial costs charged for the whole plant, depending on the load profile shape.