A resorbable 3D printed polydioxanone (PDO) device is manufactured to facilitate ligation of vascular tissue during surgery. The device must provide sufficient mechanical performance throughout the healing period. Therefore, degradation and mechanical performance of the device are investigated as a function of in vivo and in vitro aging. During aging the PDO device released cyclic and linear water‐soluble products. In vivo aging resulted in higher relative number of linear oligomers in comparison to in vitro aging. A major loss of mechanical performance is observed after only 10 days in vivo and the Young’s modulus (E) and tensile strength at break (σb) decreased by 28% and 54%, respectively. This is in contrast to in vitro aging, where no loss of mechanical properties is observed during the same period. The in vivo aged devices exhibit clear holes in the matrices after 28 days, while apparent cracks are observed first after 140 days in vitro. These results highlight the sensitivity of the degradation process of resorbable devices with regards to the interactions of the device with the surrounding environment (tissues) and demonstrate the importance of in vivo testing as compliment to in vitro testing before clinical use of devices.