Integrated power semiconductors are often used for applications with cyclic on-chip power dissipation. This leads to repetitive self-heating and thermo-mechanical stress, causing fatigue on the on-chip metallization and possibly destruction by short circuits. Because of this, an accurate simulation of the thermo-mechanical stress is needed already during the design phase to ensure that lifetime requirements are met. However, a detailed thermo-mechanical simulation of the device, including the on-chip metallization is prohibitively time-consuming due to its complex structure, typically consisting of many thin metal lines with thousands of vias. This paper introduces a two-step approach as a solution for this problem. First, a simplified but fast simulation is performed to identify the device parts with the highest stress. After, precise simulations are carried out only for them. The applicability of this method is verified experimentally for LDMOS transistors with different metal configurations. The measured lifetimes and failure locations correlate well with the simulations. Moreover, a strong influence of the layout of the on-chip metallization lifetime was observed. This could also be explained with the simulation method. Index Terms-Integrated power technologies, integrated circuit modeling, power semiconductor devices, on-chip metallization, thermo-mechanical stress, degradation, reliability.