BACKGROUND The hydrodynamic mechanisms of systolic anterior motion (SAM) of the mitral valve in hypertrophic obstructive cardiomyopathy (HOCM) remain unclear. METHODS Based on computed tomography (CT) images and clinical data, pre- and post-operative computational models of the left ventricle were constructed for 6 HOCM patients receiving septal myectomy. SAM was abolished in 5 patients and persisted in one after septal myectomy surgery. The obtained simulation results including flow field of the left ventricle and mechanical behaviors of the mitral valve (MV) between pre- and post-operative FSI models were compared. RESULTS The pressure difference and shear stress on the mitral valve leaflets (MVL) were relatively high pre-operatively, and decreased significantly after satisfactory surgery, but remained high following failed surgery. The significant increase in coaptation-to-septal distance was found when SAM was abolished. CONCLUSIONS Our results indicated that high pressure difference and shear stress on the MVL might directly initiate SAM in HOCM. Successful septal myectomy enlarged the coaptation-to-septal distance sufficiently to keep the MVL away from the ejection flow, thereby eliminating SAM.