Objectives The aim of our study was to evaluate the role of flavonoids in the improvement of post-operative symptoms after endovenous thermal ablation (EVTA). Methods A prospective comparative study of 120 consecutive patients undergoing EVTA of the greater saphenous vein associated with phlebectomies was undertaken. Patients were grouped in those receiving micronized purified flavonoid fraction (MPFF- 60 patients) agent 500 mg Bid 7 days pre- and 30 days post- operatively (MPFF group) and those in the control group (60 patients) who did not. Demographics, intra-operative details, Clinical –Etiology- Anatomy- Pathophysiology (CEAP) clinical class, 10-cm Visual Analog Scale (VAS) for pain, Venous Clinical Severity Score (VCSS) and Chronic Venous Insufficiency Quality-of-Life Questionnaire (CΙVIQ-20) were recorded. Primary outcome was the postoperative pain assessement using the VAS scale and CIVIQ pain score. Secondary outcomes included assessement of VCSS and CΙVIQ-20 scores. Results There were no significant differences between the groups regarding demographics, clinical and procedural characteristics. Patients in MPFF group reported significantly lower VAS pain levels than control group at 7- (−3.6 ± 1.2 vs −2.7 ± 1.9, p < .0001) and 30- post-operative day (−4.9 ± 0.1 vs −4.2 ± 1, p < .0001). MPFF group also showed better outcome in terms of CIVIQ pain score at 7- (−3.7 ± 1.3 vs −3.5 ± 1.8, p = .008) and 30- post-operative day (−5.3. ± 1.1 vs −4.4 ± 1, p = .017). Both groups showed a significant improvement in VAS pain score (p = .047), global CIVIQ-20 (p = .009) and VCSS (p = .008) at 7- and 30-days post-operatively. Conclusions Administration of flavonoids in patients undergoing EVTA associated with phlebectomies reduces pain by a small amount during early postoperative period.