The influence of topographical surface features at the submicron scale on the structural changes in the surface-adsorbed fibrinogen was investigated on poly(lactic-co-glycolic-acid) (PLGA) films. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) was employed in this study for the induced conformational change of fibrinogen over various adsorption times, while the adsorption kinetics of fibrinogen was quantified by the enzyme linked immunosorbent assay (ELISA). When a PLGA surface is modified topographically, the adsorbed fibrinogen undergoes less conformational change when compared to adsorption on the pristine PLGA surface. The extent of conformational change is related to platelet adhesion. Reduced thrombogenicity was demonstrated by the higher ratios of alpha-helix to beta-turn and beta-sheet to beta-turn structures on the topographic PLGA film, which suggests that topographical manipulation of surfaces is a viable approach to influence the thrombogenicity of surfaces.