The aim of this study was the evaluation of the effects of Venoruton (HR) on the prevention and control of flight microangiopathy and edema in subjects with varicose veins flying for more than 7 hours. A group of 80 patients with varicose veins, edema, and initial skin alterations due to chronic venous hypertension were included. Measurements of skin laser Doppler (LDF) resting flux (RF), PO2 and rate of ankle swelling (RAS), were made before and after the flights (within 2 hours before the flights and within 2 hours after the flights). The length of the flights was between 7 and 9 hours; all seats were in coach class. The two groups (treatment and control) were comparable for age and sex distribution. The variation (decrease) in PO2 was significant in both groups. In subjects treated with HR the decrease in PO2 was smaller (p < 0.05). The decrease in LDF-RF was significant in both groups with a higher flux at the end of the flight in the treated subjects (p < 0.05). The venoarteriolar response was decreased at the end of the flights. The decrease was less evident in the treatment group (p < 0.05). The increase in RAS was significant in the control group while it was limited in the HR group. In conclusion, HR is useful for reducing the increased capillary filtration and in controlling edema in patients with chronic venous disease in long-haul flights. HR is effective to control flight microangiopathy associated with edema.