This paper analyzes the impact of a nonuniform temperature distribution inside insulated-gate bipolar transistor (IGBT) power modules on the reliability of railway power inverters. The interaction between the chosen cooling system (a heat-pipe-based one) and the power module is considered in detail. After showing the experimental setup and thermal conditions, thermal mapping inside the power module is carried out. Then, the effects of the thermal cycles on the constitutive elements of the IGBT module are pointed out when considering a real mission profile. Finally, the experimental results from the thermal cycles are linked to problems on the power-inverter reliability. Concretely, the thermal-grease distribution is analyzed on failed IGBT modules coming from the field, and the solder-delamination pattern observed in IGBT modules after endurance cycling tests is also reported.