Ezrin, radixin and moesin possess a very similar structure with a C-terminal actin-binding domain and a N-terminal FERM interacting domain. They are known to modulate the cell cytoskeleton in several cell types, but their expression pattern is tissue specific. Their contribution to the regulation of vascular smooth muscle cells (VSMC) cytoskeleton is still unknown. The aim of this study was to investigate the expression of ERM proteins in VSMC and their role in cell migration evoked by PDGF, a growth factor involved in pathophysiological processes like angiogenesis or atherosclerosis. Primary cultured VSMC obtained from rat aorta were used. The expression of ERM proteins was determined by Western blot and was inhibited with specific siRNA. Control cells were transfected with a scramble siRNA. Cell migration was measured by the wound healing assay. The three proteins, ezrin, radixin and moesin, were detected in VSMC. Cell transfection with specific siRNAs led to an inhibition of 96 ± 2%, 99 ± 1% and 94 ± 2% of ezrin, radixin and moesin expression, respectively. In cells transfected with the three siRNA against ezrin, radixin and moesin simultaneously, total ERM proteins expression was inhibited by 98 ± 1%. In VSMC stimulated with PDGF, actin stress fibers were markedly reorganized, lamellipodia were formed and migration was increased. Simultaneous depletion of the three ERM proteins abolished the effects of PDGF on cell architecture and on migration, while depletion of ezrin, radixin or moesin only slightly modified actin cytoskeleton reorganization and did not affect migration in response to PDGF. These results indicate that ERM proteins function in a redundant manner and are involved in the migration of VSMC in response to PDGF.