Geometric cues have been used for a variety of cell regulation and tissue regenerative applications. While the function of geometric cues is being recognized, their stability and degradation behaviors are not well known. Here, we studied the influence of degradation on uniaxial-stretch-induced poly(ε-caprolactone) (UX-PCL) ridge/groove arrays and further cellular responses. Results from accelerated hydrolysis in vitro showed that UX-PCL ridge/groove arrays followed a surface-controlled erosion, with an overall geometry remained even at ∼45% film weight loss. Compared to unstretched PCL flat surfaces and/or ridge/groove arrays, UX-PCL ridge/groove arrays achieved an enhanced morphological stability against degradation. Over the degradation period, UX-PCL ridge/groove arrays exhibited an “S-shape” behavior of film weight loss, and retained more stable surface hydrophilicity and higher film mechanical properties than those of unstretched PCL surfaces. Human mesenchymal stem cells (MSCs) aligned better toward UX-PCL ridge/groove arrays when the geometries were remained intact, and became sensitive with gradually declined nucleus alignment and elongation to the geometric degradation of ridges. We speculate that uniaxial stretching confers UX-PCL ridge/groove arrays with enhanced stability against degradation in erosive environment. This study provides insights of how degradation influences geometric cues and further cell responses, and has implications for the design of biomaterials with stability-enhanced geometric cues for long-term tissue regeneration. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 2197–2207, 2014.