Dysfunction of vascular smooth muscle cells (VSMCs) is key in the pathogenesis of proliferative cardiovascular diseases, including atherosclerosis and post-angioplasty restenosis. However, to date, the molecular mechanisms of this pathological process have not been elucidated. Growing evidence indicates that microRNAs (miRNAs) are a class of novel gene regulators. Recently, miR-146a was shown to be highly expressed in rat balloon-injured vascular walls as well as in peripheral blood mononuclear cells (PBMCs) from patients with acute coronary syndrome (ACS). The aim of the present study was to investigate the role of miR-146a in regulating VSMC fate and the possible underlying mechanisms involved. Our results revealed that the expression of miR‑146a was increased in proliferative VSMCs. Subsequently, we observed that the knockdown of miR‑146a significantly inhibited the proliferative and migratory properties of VSMCs in vitro, while it markedly promoted the apoptotic capacity of VSMCs. In addition, we demonstrated that the protein expression of nuclear factor-κBp65 (NF-κBp65) and the proliferative cell nuclear antigen (PCNA), known as critical transcriptional factors, were downregulated. By contrast, the crucial proapoptotic molecule Bax has been revealed to be upregulated following miR‑146a knockdown. These results support the conclusion that miR-146a is a novel regulator of VSMC fate and may be a new biomarker or therapeutic target for proliferative cardiovascular disease.