The aim of this study was to prospectively investigate the clinical efficacy of Daflon therapy in patients with mild to moderate chronic venous insufficiency (CVI) (clinical class 1-4) and to assess the changes in venous hemodynamics by using air plethysmography (APG). Fifty-six limbs in 28 patients were studied. They all had primary venous insufficiency with no venous obstruction, and mixed deep and superficial venous incompetence was found in 64% of the limbs. There was a significant decrease in symptom score for swelling and heaviness after 6 months of Daflon therapy. The symptom score for cramps also showed improvement though it did not reach statistical significance. Pain was significantly reduced with a mean pain score of 21.8 +/- 19.3% before comparing to 10.4 +/- 20.2% after 6 months of Daflon therapy (p < 0.01). This was also associated with a decrease in mean calf circumference from 37.0 +/- 4.3 to 36.4 +/- 4.3 cm (p < 0.001). There was no significant change in the venous filling index (VFI), ejection fraction (EF), and residual volume fraction (RVF) before and after 6 months of Daflon therapy (VFI: 3.7 +/- 3.5 vs 3.4 +/- 2.5 mL/s, EF: 54.5 +/- 15.9% vs 57.7 +/- 19.7%, RVF: 41.4 +/- 19.2% vs 39.4 +/- 24.2%). The clinical improvement without associated changes in venous hemodynamics as measured by APG suggests that Daflon mainly works by modifying the microcirculatory environment not detected by APG and this microcirculatory change is associated with clinical improvement. In this regard, Daflon would be especially useful for symptomatic relief in patients with functional venous insufficiency who do not have clinical evidence of varicose veins but suffer from symptoms of venous insufficiency.