Although electrospun fibrous scaffolds have shown promise in biomedical applications, the degradation behaviors after in vitro and in vivo incubations and their correlations have not been clarified till now. The present study aims to comprehensively investigate the effects that in vitro cell inoculation and in vivo implantation have on the degradation, when compared with commonly processed degradation in buffer solutions. During the investigational time period, there was no significant difference in the degradation behaviors after incubation of fibrous mats into phosphate buffer saline, simulated body fluid and cell culture media. After cell inoculation into the degradation system, significantly higher mass loss, lower molecular weight reduction, and less significant increase in the molecular weight polydispersity were detected. The tight attachment of cells on fibers further enhanced the degradation process after cell seeding on the fibrous mats. When compared with in vitro cell-free degradation, the subcutaneous implantation of fibrous mats led to a significantly higher degradation rate at the initial stage, but slower degradation at the later stage. It was indicated that the degradation behaviors after in vivo implantation were close to those after cell culture on fibrous mats, thus providing an effective in vitro tool to predict in vivo degradation profiles of electrospun fibers. (c) 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012