Vascular smooth muscle cells (SMCs) change between a contractile-differentiated and a proliferative-dedifferentiated phenotype in response to environmental cues. Long non-coding RNAs (lncRNAs) and N6-methyladenosine (m6A) modification regulate cell fate decision. Here we used primary human pulmonary artery SMCs (hPASMCs) and assessed the expression of lncRNAs during SMCs phenotypic modulation. A lncRNA, which we refer to as Differentiation And Growth Arrest-related lncRNA (DAGAR) was increased during differentiation and we demonstrate that it is required for this process. DAGAR was m6A-modified and regulated by the m6A reader YTHDF2 in SMCs and MRC5 cells. A marked downregulation of YTHDF1-3 proteins during both SMC differentiation and MRC5 quiescence was found, consistent with the increase of DAGAR. Remarkably, YTHDF2 immunoprecipitation followed by RNA deep sequencing (RIP-Seq) displayed an enrichment of key SMC-associated transcripts, including smooth muscle myosin heavy chain (MYH11) and members of the TGF, PDGF and VEGF pathways. Knockdown of YTHDF2 induced DAGAR and SMC marker gene expression. We conclude that the lncRNA DAGAR and YTHDF2 contribute to the regulation of SMC plasticity and differentiation programs.