The results of occlusion plethysmography examination of leg veins are presented for 11 cosmonauts launched to the Russian segment (RS) of the International Space Station (ISS) for six-month space flights (SFs) at about four-year intervals. Baseline measurements made before the second launch to the ISS showed an increase in the leg volume and a decrease in venous capacity in comparison with the measurements before the first launch. Comparison of the data obtained in months 2 and 5 in two missions showed consistency of individual trends in changes in vein parameters; however, in the second mission the increases in vein capacity and compliance were less pronounced. There were no dramatic differences between the trends and dynamics of vein filling rates in microgravity during the second and the first SFs. It should be assumed that active fitness training in the interval between missions had a positive effect on the leg muscle condition and favored the diminution of the free compliance zone of the leg veins. It was found that repeated participation in six-month SFs had no negative influence on the condition of leg veins of cosmonauts, providing the maintenance of good physical fitness.