Engine maintenance costs are a major contributor to the direct operating costs of aircraft. Therefore, the minimization of engine maintenance costs per flight-hour is a key aspect for airlines to operate successfully under challenging market conditions. Minimization can be achieved by increasing the on-wing time or by reducing the shop-visit costs. Combining both provides optimum results and can only be achieved by thorough understanding of the engine. In the past, maintenance optimization was mainly an experience-based process. In this work, a novel analytical approach is presented to optimize the maintenance of commercial turbofan engines. A real engine fleet of more than 100 long-haul engines is used to demonstrate the application. The combination of advanced diagnostic and simulation methods with classical hardware-based failure analysis enables linking of overall engine performance with detailed hardware condition and, thus, an effective optimization of the overall maintenance process.