Abstract: AIM To assess the effect of myocardial contrast echocardiography (MCE)-guided percutaneous transluminal septal myocardial ablation (PTSMA) for hypertrophic obstructive cardiomyopathy (HOCM). METHODS A total of 22 consecutive HOCM patients were included. Before PTSMA treatment, target domains were determined according to conventional echocardiography. Coronary angiography was used to evaluate target blood vessels from the septal branch of the coronary artery. These vessels were then confirmed by MCE. After 1 month, 3 months, and 1 year, echocardiographic parameters, brain natriuretic peptide, and clinical symptoms were reassessed. RESULTS Myocardial imaging parts by MCE were in conformity with the target domains in 19/22 cases who were assigned for PTMSA. Two cases had myocardial imaging parts smaller than the primary target domains; thus, the target vessels were changed before PTMSA. One patient was rejected for PTMSA due to myocardial imaging of non-target domain. Immediate resting left ventricular outflow tract pressure (LVOTPG) decreased by >50% in 21 patients after PTMSA. Significant improvement was observed in interventricular septum thickness (IVST), mitral valve regurgitation, former systolic mitral valve motion, and brain natriuretic peptide. One-year follow-up showed that cardiac functions enhanced in these patients. CONCLUSION Percutaneous transluminal septal myocardial ablation by MCE can accurately determine target domain, select target blood vessels, quantitatively ablate focus, significantly reduce IVST/LVOTPG and ameliorate clinical symptoms in patients with HOCM.