The effects of residual stress and film thickness on crack evolution in metallic trilayers deposited on polyimide substrate have been investigated during uniaxial tensile loading. Four different systems, consisting of Mo/Cu/Cr layers deposited on polyimide, with nominal thicknesses of 100/100/100 or 100/500/100 nm, were developed using two physical vapor deposition techniques, resulting in opposite as-deposited high residual stress for the top Cr layer (about +2.7 GPa versus -2.6 GPa). First, it was found that the higher the compressive residual stress of the top Cr layer and the thickness of the middle Cu layer, the higher the critical strain to initiate crack propagation in the trilayer film system. Second, it was found that the higher the compressive residual stress of the top Cr layer and the thickness of the middle Cu layer, the lower the maximum crack density in the trilayers. The maximum crack density in the thicker system with Cr in a tensile residual stress was similar to the maximum crack density in the thinner system with the Cr top layer in a compressive residual stress.