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Fatigue is a cause of failure for micrometer-scale polycrystalline silicon devices subject to a large number of stress cycles during their operation life. Several studies in the last 15 years evidenced delayed failures happening for repetitive applied stresses as low as 50% of the nominal tensile strength. This phenomenon is surprising (polysilicon is a brittle material), and many theories were proposed for its explanation: Although different, all of them agree in that there is a strong dependence on the environmental conditions in which the device is operating. In this paper, a comprehensive study of fatigue on an industrial technology (Thick Epi-Poly Layer for Microactuators and Accelerometers process from STMicroelectronics) is presented to provide guidelines for the design of reliable large-scale devices (accelerometers, gyroscopes, magnetometers, etc.), taking into account fatigue as a reliability issue. The study compares the behavior of devices operating in ambient environment with respect to devices operating in industrial packages, where concentrations of gases are different and, in particular, the percentage of oxygen and water vapor is controlled. It is experimentally shown that the behavior is impressively different, and thus, different guidelines must be followed in the design of devices, depending on their final packaging condition.