Composite films of poly(lactic-co-glycolic-acid) with multi-walled carbon nanotubes (PLGA-MWCNT) having two different nanotube orientations, namely random and vertically aligned, have been fabricated and characterized. The effect of these nanostructured surfaces on platelet adhesion is evaluated. In particular, the thrombogenicity of the nanostructured composite films is compared with that of pristine graphite (a low thrombogenic material) and PLGA film, in order to determine the influence of surface chemistry and topography on platelet adhesion. The results in this study show that the PLGA-MWCNT composite with vertically aligned nanotubes exhibits very low levels of fibrinogen adsorption and platelet adhesion, which can be attributed to both chemical and topographical effects. Platelet adhesion shows a good correlation with the presence of COOH groups and appears to be sensitive to the topographic features of the composite films. The results in this study suggest that in addition to chemistry, nanotopographical surface modifications could be an effective strategy in the development of low thrombogenic and hemocompatible materials.