We developed a novel minimally invasive transapical beating-heart septal myectomy (TA-BSM) procedure for patients with midventricular obstruction (MVO), without the aid of cardiopulmonary bypass. This study aims to describe the TA-BSM procedure for the relief of MVO and to detail the clinical outcomes in these patients.Sixty-one patients receiving TA-BSM for MVO were included: isolated MVO (n = 12) and combined MVO and subaortic obstruction (n = 49). We reviewed the electronic medical record to collect information on preoperative, intraoperative, and postoperative parameters.The intraventricular pressure gradient after the resection was largely attenuated. On the catheter measurement, the median resting and provoked gradient decreased by 29.0 and 71.0 mm Hg, respectively. Likewise, the resting intraventricular gradient was successfully reduced from 58.0 to 11.0 mm Hg, and the maximal intraventricular gradient was reduced from 88.0 to 20.0 mm Hg at 6 months follow-up. In addition, all patients showed significantly improved MR and 37 of 42 patients with preoperative MR grade ≥2+ showed MR grade ≤1+ after TA-BSM. During the follow-up, no death was observed and no one had HCM-related rehospitalization. All patients reported improvement in symptoms and the mean New York Heart Association class improved from 3.0 (IQR, 3.0-3.0) preoperatively to 1.0 (IQR, 1.0-1.0) at 6 months follow-up.The TA-BSM procedure is a valuable therapy to relieve MVO, improving hemodynamics and providing satisfactory clinical outcomes. The procedure can also preserve favorable outcomes for patients with MVO and concomitant subaortic obstruction.© 2024 The Authors. Published by Elsevier Ltd.