Chronic venous insufficiency (CVI) is a disease characterized by failure of the venous valves that allow blood from the lower limbs to return to the heart. The more severe types of CVI (C4b-C6 disease) significantly influence patients' quality of life (QOL). The treatment options for CVI of the deep system are limited. The present study is the first-in-human study using a prosthetic venous valve, VenoValve, to initially evaluate patient outcomes. We evaluated the feasibility, initial safety, and performance outcomes of the VenoValve.