<p indent="0mm">The gravity-induced hydrostatic pressure gradient in the cardiovascular system is altered under the aerospace condition of weightlessness, leading to the increase of returned blood volume, and thus changes in cardiac structure and function. However, the characteristics and compensatory mechanisms are still unclear. The present study was to investigate the characteristics and compensatory mechanisms of cardiac preload and function in simulated acute aviation negative gravity and space microgravity using two-dimensional echocardiographic speckle-tracking strain imaging, and to provide theoretical evidence for aerospace heart protection. A total of 27 healthy young male volunteers were recruited. The tilting table was used to simulate acute microgravity (0.87~0 G) and negative gravity (0~−0.87 G). The left heart volumes, strain and functional parameters were collected and analyzed by both conventional and speckle tracking echocardiography. The systemic vascular resistance, compliance and ventricular-arterial coupling were calculated. The results showed that, the left heart volume and strain, left atrial emptying fraction and left ventricular ejecting fraction were all increased as gravity decreased. The arterial compliance was increased and the ventricular-arterial coupling index was decreased within the normal range. Of note, the reservoir, conduit and contraction function of left atrial strain were elevated proportionally; the flow velocity of left ventricular filling during early and late diastolic phases were both increased at the constant ratio. That is, the compensatory pattern was characterized by proportional improvement of cardiac motion in different phases and directions, which is different from that in aging and diseases. The present study demonstrated that the heart of healthy young men can effectively compensate the increase of preload caused by simulated acute microgravity and negative gravity. The major compensatory mechanism is the proportional improvement of myocardial motion of left atrium and ventricle during different phases (early and late diastole, systole) and along different directions (longitudinal and circumferential). The findings suggest that the aviators or astronauts generally have enough cardiac systolic/diastolic reserve to counter the acute change of cardiac preload induced by weightlessness (−0.87~1 G).