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This paper addresses the behavior of thin-film metal coated flexible substrates under high cyclic bending fatigue loading. Polyethylene terephthalate (PET) and polyethylene naphthalate (PEN) are widely used substrates in the fabrication of microelectronic devices. Factors affecting the fatigue life of thin-film coated on a flexible PET substrates were studied, including thin-film thickness, film material, bending radius, temperature, and humidity. A series of experiments for sputter-deposited copper and aluminum coated on a PET substrate were conducted. Electrical resistance and crack growth rate were monitored during the experiments at specified time intervals. In addition, a finite element model was built to simulate the bending of thin-films on flexible substrate structure. Layered shell elements were used in the model. Stress intensity and stress distribution across the film were obtained and compared with the experiments. Initial results of copper-coated PET showed a great agreement between the model and the experimental results.