Varicose veins (VVs) are a common disorder of venous dilation and tortuosity, but the underlying mechanism is unclear. The functional integrity and phenotypic differences of VVs are also unclear. This study tested the hypothesis that phenotypic and functional differences exist between smooth muscle cells (SMCs) derived from VVs and normal veins. SMCs were isolated from 28 samples of varicose great saphenous veins (VGSVs) and normal great saphenous (NGSVs) and cultured. Proliferation, migration, adhesion, and aging capacity in SMCs were compared in the two veins. Bas, Bcl-2, caspase-3, matrix metalloproteinase (MMP)-2 MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 messenger (m)RNA expression and protein content were detected by fluorescence quantitative polymerase chain reaction and immunoblotting. The microfilament structure of the framework was increased in SMCs in the VGSV group. Proliferation, migration, adhesion, and the aging cell count in SMCs in the VGSV group were significantly higher than the corresponding regions in the NGSV group (P < .05). Bas and caspase-3 mRNA expression and protein content were decreased, whereas Bcl-2 mRNA expression and protein content were increased in the VGSV group compared with the NGSV group (P < .05). MMP-2, MMP-9, TIMP-1, and TIMP-2 mRNA expression and protein content in the VGSV group were increased compared with the NGSV group (P < .05). SMCs derived from VGSVs are more dedifferentiated and demonstrate increased proliferative and synthetic capacity. These results suggest the presence of phenotypic and functional differences between SMCs derived from VGSVs and NGSVs. The phenotypic and functional abnormalities in SMCs may be associated with the pathogenesis in VGSVs.