Medium-voltage conversion systems, such as traction and grid-connected converters, are continuously evolving toward higher power densities. Consequently, volume, weight, and material reductions are becoming major design issues, which lead the research focus toward high-/medium-frequency isolated power conversion systems. An optimized design of these conversion systems requires a detailed transformer-loss evaluation considering both copper and core losses. This paper presents a simple and flexible methodology to analyze global medium-frequency transformer losses in an isolated DC-DC converter fed by general nonsinusoidal waveforms. Various loss evaluation approaches are considered, pointing out their validity and limitations by means of finite-element simulations and experimental tests.