Objective Mitogen Inducible Gene 6, Mig-6 is identified as a negative feedback inhibitor of epidermal growth factor receptor (EGFR) signal. The Molecular targets of neointima formation still have not been fully addressed. We investigated the effect of Mig-6 gene ablation in vascular smooth muscle cell (VSMC) and its role in intimal hyperplasia. Methods Conditional ablated Mig-6 in the VSMC was generated using the Tagln-Cre mouse model (Tagln^cre/+Mig-6^f/f; Mig-6^d/d). To investigate the neointima formation, we used balloon injury mouse model. Primary cultured VSMCs were obtained from 10-week-old Mig-6^f/f and Mig-6^d/d male mice for immunoblotting, proliferation and migration assays. Results The neointima formation of injured artery was significantly enhanced in the Mig-6^d/d mice compared to Mig-6^f/f after balloon injury. Primary cultured Mig-6^d/d VSMC caused a significant increase in the proliferative and migratory capability of the cells compared to Mig-6^f/f. EGF, Angiogensin II and SDF1 stimulation in the primary cultured Mig-6^d/d VSMC increased growth and motility. Furthermore, angiotensin II receptor blocker and inhibitors of EGFR, PI3K and MAPK reversed these enhanced proliferation and migration of primary cultured Mig-6^d/d VSMC. On western blotting, the increased phosphorylation of EGFR was observed in primary cultured Mig-6^d/d VSMC compared to Mig-6^f/f. Conclusion We found that neointima formation was augmented in the VSMC specific Mig-6^d/d mice. Mig-6 plays an important role in determining growth and motility of VSMC. Therefore, we suggest that Mig-6 may provide a new insight into development of more effective ways for the treatment and prevention of neointima formation.