Hybrid desiccant HVAC systems have shown several advantages, compared to conventional cooling and dehumidification systems. Therefore, their use is also spreading for tertiary and residential buildings, especially when the regeneration of the desiccant can be obtained by using available waste heat. In this paper, an experimental analysis is presented on the performances of a silica-gel desiccant wheel, inserted in a test facility characterized by an advanced desiccant air handling unit, coupled to an electric chiller, a natural gas-fired boiler and a small scale cogenerator. The desiccant wheel is regenerated by using low temperature thermal energy recovered from the microcogenerator. The effects of the main thermal-hygrometric parameters (outdoor air humidity ratio and temperature, regeneration air temperature) on the desiccant wheel performances have been experimentally evaluated; in particular, the thermal-hygrometric properties of the process air exiting the rotor and the desiccant wheel effectiveness values have been obtained. Finally, fixing the regeneration temperature at its maximum available value (65 °C), ventilation and internal latent loads that the desiccant wheel can handle have been evaluated and compared to the required values, both for a set of cities all over the world and as a function of the thermal-hygrometric outdoor conditions.