INTRODUCTION: We previously reported the clinical benefits of radiofrequency catheter ablation (RFCA) of premature ventricular contractions (PVCs) from the right ventricular outflow tract or near His-bundle, which often can deteriorate clinical status and cause left ventricular (LV) dilation that develops into heart failure. This study aimed to evaluate the role of ablating PVCs per RFCA from a trans-interatrial septal approach in the LV dilation and clinical status in patients with PVCs from the mitral annulus (MA) (MA-PVCs) without structural heart disease. METHODS: The frequency of PVCs per the total heart beats by 24-h Holter monitoring, left ventricular ejection fraction (LVEF) and left ventricular end-diastolic (LVDd) and -systolic (LVDs) internal dimensions by echocardiography, New York Heart Association (NYHA) functional class, and serum brain natriuretic peptide (BNP) concentration in 22 patients with MA-PVCs were evaluated before and 6 months after RFCA. RESULTS: Before the RFCA, the patients with frequent (20% <) PVCs demonstrated a significantly reduced LVEF, enlarged LVDd and LVDs, deteriorated NYHA functional class, and elevated serum BNP concentration as compared to the subgroup with rare (≤ 20%) PVCs. Furthermore, ablating MA-PVCs readily produced an improvement in those abnormalities as compared to that before the RFCA. Interestingly, the MA-PVCs were successfully ablated from not only the ventricular side of the MA (68%) or coronary sinus (5%), but also the left atrial side of the MA (18%). CONCLUSIONS: RFCA produces clinical benefits in patients with MA-PVCs. Further, it may be necessary to initially consider a trans-interatrial septal approach to ablate these PVCs.