Objective To investigate the transient hemodynamic changes during balloon deflation in coronary interventional operation, so as to explore the potential influence of balloon deflation on the occurrence of post-operative no-reflow. Methods An in vitro experimental apparatus was built, in which a high-speed camera was used to take snapshots of balloon deformation and flow field (marked by dyed water) during balloon deflation. Subsequently, image processing techniques were employed to derive the parameters of balloon deformation and estimate the flow velocity downstream from the balloon. A computer model of the experimental apparatus was constructed, with the incorporation of the measured balloon deformation data, to simulate the balloon deflation process under various perfusion pressure and fluid conditions. Results The balloon exhibited a highly nonlinear deformation behavior during deflation. The measured and simulated flow velocities downstream from the balloon were in reasonable agreement, both manifesting a monotonic increase with post-deflation time and perfusion pressure. Numerical simulations further revealed that when the flow velocity downstream from the balloon approached the physiological value of blood flow velocity in the coronary artery, the flow velocity in the balloon-vessel gap and wall shear stress (WSS) reached up to 8-10 times and 60-70 times of their physiological values, respectively. Conclusions Balloon deflation led to a sharp acceleration of flow in balloon-vessel gap and a concomitant abnormal rise in WSS, which might promote the stripping of plaque or thrombus flakes. In view of the fact that the balloon deflation-induced rise in WSS was augmented by the increase in perfusion pressure, taking strategies such as lowering pre-operative blood pressure or implementing balloon deflation during diastole in coronary interventional operation might help to reduce the risk of no-reflow.