A hydraulic power-assist system is a hydraulic regeneration system that can significantly improve fuel economy when installed on a conventional bus operating in urban traffic. This paper presents a methodology for matching a new hydraulic power-assist system (HPA) to a conventional bus. The HPA and the conventional bus were modeled using the AMESim environment. The HPA was optimized using a simulation-based orthogonal design method with two indexes, the fuel economy and the acceleration performance. According to the simulation results, the volume of the accumulator was the primary factor affecting fuel economy, and the gear ratio of the transfer case was the primary factor influencing the acceleration performance. As a result, tradeoffs between the two indexes are required for a practical operational scenario. Experimental results demonstrated that the optimal HPA installed on a conventional bus was able to satisfy the acceleration performance requirement of the vehicle and also reduced fuel consumption by 25 percent.