Left ventricular stimulation for cardiac resynchronization therapy is largely limited by access and anatomy of coronary veins.This study sought to apply ultrasound-mediated leadless pacing technology in heart failure patients and to evaluate the effects of respiration and body posture on the acoustic window.Patients with advanced heart failure and ejection fraction ≤35% were studied. An electrophysiology catheter incorporating a receiver electrode to deliver ultrasound-mediated pacing was positioned in the left ventricle. Ultrasound-mediated pacing thresholds were determined. The acoustic windows on the chest wall with the patient lying supine, titled 30° leftward, 30° rightward, and 30° upward were determined. The acoustic windows were also determined with computed tomography and transthoracic echocardiography. Simulated receiver movement with respiratory movement and body positioning was assessed with computed tomography.Ten patients were studied. Ultrasound-mediated pacing was successful in all patients. The acoustic window measured 39.6 ± 18.2 cm 2 . The window size decreased with rightward tilt, and increased with leftward and upward tilt. They correlated with measurements made by transthoracic echocardiography and computed tomography. Target receiver movement of 1.2 ± 1.4 cm horizontally and 1.3 ± 0.8 cm vertically were estimated by computed tomography.The feasibility of leadless left ventricular stimulation was shown acutely in heart failure patients. The acoustic window validated by computed tomography was predicted by transthoracic echocardiography. Effects of respiration and body posture were evaluated for development of the future implantable device.