OBJECTIVE: This study validates the off-pump antegrade trans-ventricular route for ultrasound-guided direct access aortic valve replacement. Direct access aortic valve replacement using a transthoracic and valved stent-based approach offers numerous advantages over the remote access percutaneous approach and may one day provide an alternative treatment modality for aortic valve disease. METHODS: Valved stents were implanted off-pump in 17 pigs (72.10+/-8.4 kg) via the direct access transapical approach using a left-sided mini-thoracotomy and continuous ultrasonic and fluoroscopic guidance. Acute valved stent function was studied with intravascular and two-dimensional intracardiac ultrasound. The invasive valve gradient was assessed with pull-back pressure catheter. All valved stents were tested in vitro before insertion. Macroscopic analysis was performed at necropsy. RESULTS: In 11 of the 17 pigs, valved stents were delivered to the target site over the native aortic valve leaflets without interference of coronary blood flow and with good acute valve function. Three valved stents were deployed supra-annularly, two of those occluded the right coronary orifice and one the left coronary orifice, leading to fatal outcomes. Three valved stents dislodged into the left ventricle, one because of size-mismatch and two because of failure to unfold correctly. In 11 properly sized and deployed valved stents, two showed a moderate and one a severe paravalvular leak. CONCLUSIONS: Seventeen pigs underwent direct access valve replacement of the aortic valve with deployment of a valved stent into the native aorta. Eleven valves observed for an average 5-h period showed satisfactory, postimplantation valve function.