The objectives were to evaluate cardiac and peripheral changes induced by microgravity with and without countermeasures (CM), to assess the peripheral response to orthostatic tests (tilt, LBNP). Inflight or HDT, we used echography and Doppler to assess the left heart function and the peripheral arteries. We studied the cardiovascular system during 1) 21-d and 25-d spaceflights without CM, 2) 14-d spaceflight with “bracelets” CM, 3) 28-d HDT with and without LBNP, and 4) 30-d HDT with and without Exercise+LBNP. Similar peripheral circulation changes were noticed in both astronauts and HDT subjects without CM. There was a decrease in renal, cerebral, and femoral vascular resistances and maintenance of cerebral flow at rest, and a lack of increase in lower limb vascular resistance and abnormal flow redistribution during orthostatic tests. Conversely, with CM at rest, cerebral and renal vascular resistances stayed elevated and femoral resistance decreased, but less than without countermeasures. Lower limb vascular resistance increased normally, peripheral flows were adequately redistributed during orthostatic tests, and no orthostatic intolerance was observed. This confirms the efficiency of countermeasures (LBNP, exercise, cuffs) in preserving the vasomotor tone in most peripheral areas at rest and reducing the development of orthostatic intolerance.