The mass loss behavior of degradable tissue scaffolds is critical to their lifespan and other degradation-related properties including mechanical strength and mass transport characteristics. This paper presents a novel method based on synchrotron imaging to characterize the scaffold mass loss from erosion degradation in situ, or without the need of extracting scaffolds once implanted. Specifically, the surface-eroding degradation of scaffolds in a degrading medium was monitored in situ by synchrotron-based imaging; and the time-dependent geometry of scaffolds captured by images was then employed to estimate their mass loss with time, based on the mathematical model that was adopted from the literature of surface erosion with the experimentally-identified model parameters. Acceptable agreement between experimental results and model predictions was observed for scaffolds in a cylindrical shape, made from poly(lactic-co-glycolic) acid (PLGA) and polycaprolactone (PCL). This study illustrates that geometry evaluation by synchrotron-based imaging is an effective means to in situ characterize the scaffold mass loss as well as possibly other degradation-related properties.