Flexible electronics are electronic devices and components that can be stretched, bent, twisted, and folded without losing their functionality. Flexible electronics is conformable, lightweight, easily tailorable, and low-cost, and thus, flexible electronics is increasingly being explored in health care, internet of things, automotive, aerospace, communication, safety, security, and food-related applications. Also, flexible electronics can now support increased functionality as well as various fabrication techniques. With an increased adaptation of flexible electronics, research is being conducted to better understand the failure mechanism of flexible electronics and thus improve their reliability and service life. In this paper, a cyclic mandrel bend test has been designed and carried out on printed conductors with PET and PI substrates. With the designed test apparatus, both tensile and compressive bend tests have been performed. Using a four-wire method, the resistance change of the printed conductors with different widths has been measured in situ under tensile and compressive loading conditions using mandrels with different radii. The results have been compared among different conductor widths, bending modes, and substrate materials. Besides, in situ SEM images have been taken to understand the failure mechanisms of the printed conductors. Based on the study, it is seen that there exists a direct correlation between the mandrel diameter, the damage in the printed conductor, and thus, the resistance change with cyclic mandrel testing. Also, it is seen that the damage under compressive bending mode is significantly lower than the damage under tensile bending mode.