In this paper, we comprehensively investigate the fatigue life and the failure modes of horseshoe-patterned stretchable interconnects, through both experimental and numerical analysis. The experimental results demonstrate that the fatigue life of a horseshoe-patterned stretchable interconnect embedded into a silicone matrix is able to resist up to 3000 cycles for a uniaxial elongation of 10%. By increasing the magnitude of the uniaxial elongation up to 30%, the lifetime drops rapidly to 85 cycles. A power law curve fitting relating the elongation versus the number of stretching cycles (E-N curve) is proposed based on the above mentioned experimental results. Moreover, combining the numerical modeling with the experimental results, a modified Coffin-Manson equation for fatigue life prediction is proposed for further evaluation of reliability performance. Micrographs and the correlated numerical simulations of the non-encapsulated stretchable intereconnects provide the experimental evidences and numerical explanations of the three-step failure processes.