The paper presents the results of investigating the lower limbs venous status in cosmonauts (n = 13) with the use of occlusion plethysmography in 6-month missions to the Russian segment of the International space station (ISS). An interrelation of shifts in venous capacitance, compliance and filling with orthostatic tolerance (OT) in the lower body negative pressure test (LBNP) was stated. OT predictability by the leg vein status in the course of space flight was demonstrated. The objective changes of veins predictive of OT reduction were identified. There are 3 levels of changes in venous capacitance, compliance and filling that prognosticate respective reductions in LBNP tolerance and were attested in 91% of the in-flight LBNP testing.