•A comprehensive simulation model has been developed to predict the overall energy performance of PV-DSF.•Sensitivity analyses of air gap depths were conducted and the optimal air gap depth was identified.•The overall energy performance and energy saving potential of the PV-DSF was evaluated.•A comparative study was conducted between the PV-DSF and other commonly used window technologies. This paper presents the annual overall energy performance and energy-saving potential of a ventilated photovoltaic double-skin facade (PV-DSF) in a cool-summer Mediterranean climate zone. A numerical simulation model based on EnergyPlus was utilized to simulate the PV-DSF overall energy performance, simultaneously taking into account thermal power and daylight. Based on numerical model, sensitivity analyses about air gap width and ventilation modes have been lead in Berkeley (California) with the aim to optimize unit’s structure design and operational strategy of PV-DSF. Via simulation, the overall energy performance including thermal, power and daylighting of the optimized PV-DSF was evaluated using the typical meteorological year (TMY) weather data. It was found that per unit area of the proposed PV-DSF was able to generate about 65kWh electricity yearly. If high efficiency cadmium telluride (CdTe) semi-transparent PV modules are adopted, the annual energy output could be even doubled. The PV-DSF studied, also featured good thermal and daylighting performances. The PV-DSF can effectively block solar radiation while still providing considerable daylighting illuminance. Due simply to excellent overall energy performance, a PV-DSF at Berkeley can reduce net electricity use by about 50% compared with other commonly used glazing systems. Efficiency improvements of semi-transparent PV modules would further increase the energy saving potential of a PV-DSF and thus making this technology more promising.