Background. Chronic venous disease (CVD) is one of the most common disorders of peripheral vessels. The search for an optimal treatment option is a challenging issue. Micronized purified flavonoid fraction (MPFF) is expected to act on the different mechanisms involved in CVD pathogenesis. Considering the high prevalence of CVD in general population, its significant impact on health-related quality of life in both younger and older patients, this study was brought up to study the effects of pharmacotherapy with MPFF and invasive treatment with EVLA, either alone or in combination, on the key serum biomarkers of vascular inflammation and remodeling, and patient quality-of-life (QoL). Objective. To study the effects of MPFF, EVLA, and the combination on vein-specific inflammatory biomarkers QoL in CEAP C2-C3 patients with varicose veins. Methods. In this prospective cohort study all subjects (N=95) received compression therapy and were allocated non-randomly to: control (compression only); MPFF; EVLA without adjuvant MPFF; and EVLA plus MPFF. Serum levels of E-selectin, MCP-1, VEGF, MMP-2 were measured, and a QoL questionnaire (CIVIQ-20) performed. Results. Treatments were associated with significant reductions in inflammatory biomarkers including E-selectin, MCP-1, and VEGF for MPFF (p<0.001), and E-selectin, MCP-1 and MMP-2 for EVLA (p<0.001). MPFF plus EVLA was associated with reductions in all studied biomarkers (p<0.001). CIVIQ-20 was improved by 23%, 29%, 36% and 40% at 2 months in the compression only, MPFF, EVLA, and EVLA plus MPFF groups, respectively. Conclusion. Reductions in serum biomarkers and improvement in QoL appeared greatest among patients treated with EVLA plus MPFF. Highlights: MPFF improves biochemistry and quality of life in chronic venous disease