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IntroductionThere is no consensus regarding the benefits of venoactive or venotonics drugs such as Micronized Purified Flavonoid Fraction (MPFF) after endovenous therapy. This study aims to address this gap by systematically reviewing the effects of venotonic drugs after endovenous treatments.MethodsA systematic review was conducted, encompassing all relevant studies published up to September 1st 2024. The inclusion criteria were as follows: (1) Initiation of a venotonic drug within 4 weeks or on the same day as undergoing endovenous therapy for lower limb veins; (2) The dosage of venotonic was specified; (3) Any classification of Clinical-Etiology-Anatomy-Pathophysiology (CEAP) was included. Exclusion criteria involved studies that focused solely on the effects of venotonics without the use of endovenous therapy techniques.ResultsSeven studies (four randomized controlled trials, and three cohort studies) involving 1703 (85.9% female) participants were included. The weighted mean age was 41.7 years. Six studies used MPFF, while one study used a combination of diosmin + Centella asiatica+vitamin C. Participants spanned CEAP classifications C1 to C61, with the majority 1210 (71.1%), classified as C1. MPFF showed significant benefits in nine (75.0%) out of 12 assessments when assessed using visual analog scale for pain.ConclusionThe combination of MPFF or diosmin + Centella asiatica + vitamin C with endovenous therapy has been shown to improve pain scores and quality of life compared to groups not receiving venotonics. No studies reported any detrimental effects. However, to establish definitive recommendations regarding the use of venotonics, further randomized, placebo-controlled trials are needed.