The aim of this study was to investigate an in vivo tissue response to a biodegradable polyesterurethane, specifically the cellular and angiogenic response evoked by varying implant architectures in a subcutaneous rabbit implant model. A synthetic biodegradable polyester-urethane was synthesized and processed into three different configurations: a non-porous film, a porous mesh and a porous membrane. Glutaraldehyde cross-linked bovine pericardium was used as a control. Sterile polyesterurethane and control samples were implanted subcutaneously in six rabbits (n = 12). The rabbits were killed at 21 and 63 days and the implant sites were sectioned and histologically stained using haemotoxylin and eosin (H&E), Masson's trichrome, picosirius red and immunostain CD31. The tissue-implant interface thickness was measured from the H&E slides. Stereological techniques were used to quantify the tissue reaction at each time point that included volume fraction of inflammatory cells, fibroblasts, fibrocytes, collagen and the degree of vascularization. Stereological analysis inferred that porous scaffolds with regular topography are better tolerated in vivo compared to non-porous scaffolds, while increasing scaffold porosity promotes angiogenesis and cellular infiltration. The results suggest that this biodegradable polyesterurethane is better tolerated in vivo than the control and that structural variants of biodegradable polyester-urethane in vivo evoke a cellular and angiogenic response that is dictated by architecture. (C) 2008 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.