In the present context of the global economic crisis and environmental emergency, transport science is asked to find innovative solutions to turn traditional vehicles into fuel-saving and eco-friendly devices. In the last few years, hybrid vehicles have been shown to have potential benefits in this sense. In this paper, the fuel economy of series hybrid-electric and hybrid-mechanical buses is simulated in two real driving situations: cold and hot weather driving in the city of Taranto, in Southern Italy. The numerical analysis is carried out by an inverse dynamic approach, where the bus speed is given as a velocity pattern measured in the field tests performed on one of the city bus routes. The city of Taranto drive schedule is simulated in a typical tempered climate condition and with a hot temperature, when the air conditioning system must be switched on for passenger comfort. The fuel consumptions of hybrid-electric and hybrid-mechanical buses are compared to each other and with a traditional bus powered by a diesel engine. It is shown that the series hybrid-electric vehicle outperforms both the traditional and the mechanical hybrid vehicles in the cold weather driving simulation, reducing the fuel consumption by about 35% with respect to the traditional diesel bus. However, it is also shown that the performance of the hybrid-electric bus gets dramatically worse when the air-cooling system is continuously turned on. In this situation, the fuel consumption of the three different technologies for city buses under investigation is comparable.