In vascular tissue engineering, three-dimensional (3D) biodegradable scaffolds play an important role in guiding seeded cells to produce matrix components by providing both mechanical and biological cues. The objective of this work was to fabricate fibrous biodegradable scaffolds from novel poly(ester amide) s (PEAs) derived from L-alanine by electrospinning, and to study the degradation profiles and its suitability for vascular tissue-engineering applications. In view of this, L-alanine-derived PEAs (dissolved in chloroform) were electrospun together with 18-30% w/w polycaprolactone (PCL) to improve spinnability. A minimum of 18% was required to effectively electrospin the solution while the upper value was set in order to limit the influence of PCL on the electrospun PEA fibres. Electrospun fibre mats with average fibre diameters of similar to 0.4 mu m were obtained. Both fibre diameter and porosity increased with increasing PEA content and solution concentration. The degradation of a PEA fibre mat over a period of 28 days indicated that mass loss kinetics was linear, and no change inmolecular weight was found, suggesting a surface erosion mechanism. Human coronary artery smooth muscle cells (HCASMCs) cultured for 7 days on the fibre mats showed significantly higher viability (p<0.0001), suggesting that PEA scaffolds provided a better microenvironment for seeded cells compared with control PCL fibre mats of similar fibre diameter and porosity. Furthermore, elastin expression on the PEA fibre mats was significantly higher than the pure PEA discs and pure PCL fibre mat controls (p<0.0001). These novel biodegradable PEA fibrous scaffolds could be strong candidates for vascular tissue-engineering applications. Copyright (C) 2012 John Wiley & Sons, Ltd.