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The applications of poly (lactide-co-glycolide) acid (PLGA) for coating or fabricating polymeric biodegradable stents (BDSs) have drawn more attention. The fluid shear stress has been proved to affect the in vitro degradation process of PLGA membranes. During the maintenance, BDSs could be suffered different patterns of fluid shear stress, but the effect of these different patterns on the whole degradation process is unclear. In this study, in vitro degradation of PLGA membranes was examined with steady, sinusoid, and squarewave fluid shear stress patterns in 150 mL deionized water at 37°C for 20 days, emphasizing on the changes in the viscosity of the degradation solution, mechanical, and morphological properties of the samples. The unsteady fluid shear stress with the same average magnitude as the steady one accelerate the in vitro degradation process of PLGA membranes in terms of maximum fluid shear stress and "window" of effectiveness. Maximum fluid shear stress accelerates the in vitro degradation of molecular fragments that diffused out in the solution while the "window" of effectiveness affects too in the early stage. Besides, maximum fluid shear stress and "window" of effectiveness accelerates the in vitro loss of tensile modulus and ultimate strength of the PLGA membranes while the maximum fluid shear stress plays the leading role in the decrease of tensile modulus at the early degradation stage. This study could help advance the degradation design of PLGA membranes under different fluid shear stress patterns for biomedical applications like stents and drug release systems. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 23-30, 2017.