The aim of this study was to evaluate the clinical efficacy of standardized French maritime pine bark extract Pycnogenol in patients with severe chronic venous insufficiency (CVI). 98 subjects with symptomatic CVI and edema were randomly assigned to one group treated with 150 mg Pycnogenol a day only, another group with stockings only and a third group with both Pycnogenol and elastic stockings. The average ambulatory venous pressure (AVP) at inclusion was 58+/-7 mm Hg (range 48-60 mm Hg) with a refilling time (RT)<12 s (average 7+/-2 s). The duration of the disease was on average 6.0+/-3.1 years. There were no differences in AVP or RT among the 3 groups at inclusion and microcirculatory and clinical evaluations were comparable. After 8 weeks treatment there was a significant decrease of rate of ankle swelling, resting flux, transcutaneous pO(2) and clinical symptom scores in all groups with significantly better results for the combination treatment. Pycnogenol alone was more effective than compression alone for all parameters (p<0.05). No side-effects were observed; compliance and tolerability were very good. This study corroborates a significant clinical role for Pycnogenol in the management, treatment and control of CVI also in combination with compression.