Background: Varicose veins (VV) pathogenesis is multifactorial and has been attributed to both genetic and epigenetic factors. Vein wall dilation occurs concurrently or because of the venous hypertension and inflammation, further exacerbating the venous reflux. These effects are due to changes in the endothelium (ECs) and smooth muscle cells (SMCs), and their impaired cross-talk that play an important role in venous constriction. Due to limited access to ECs and SMCs from patients, the molecular mechanisms underlying vascular dysfunction in VV remain largely unknown.Induced pluripotent stem cells (iPSCs) provide a unique platform to recapitulate the disease phenotype in vitro thereby allowing unprecedented access to patient-specific cells. iPSCs derived from somatic cells possess the ability to differentiate into multiple cell types, including protein expressing ECs and SMCs. Furthermore, iPSC-derivatives are patient-specific, i.e., the encoded proteins are dictated by the genome of the original somatic donor cell. Goals: By creating iPSCs from VV patients, we can model and characterize to recapitulate the disease phenotype. With these efforts, our goal is to elucidate the underlying disease mechanisms and validate the candidate genes that are, in part responsible for VV. Methods: We have recruited 32 VV patients in our Stanford clinic. Peripheral blood mononuclear cells (PBMCs) are to be isolated. Patient-specific iPSC lines are generated from patients with VV and differentiated to ECs and SMCs. Results: Our lab has developed a robust, chemically defined monolayer differentiation protocol for iPSC-ECs that consistently yields about 80-95% CD31+ cells. Using this approach, I differentiated iPSCs from both the control and VV patients to ECs. The expression of specific cell type markers (PECAM1, NOS3, CDH5, VWF) were determined by RT-qPCR. Conclusion: Our patient-specific iPSC will become possible to model individual responses to treatment and medications and to find variants that lead to differences in outcomes. However, the clear demarcation between venous and arterial phenotypes was not assessed. Therefore, our future strategies will determine the functional and developmental differences between venous and arterial iPSC-ECs.