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We report our experience with the CardiAQ prosthetic valve using both transapical and transseptal access. Aim of our study was proving the feasibility, safety and effectiveness of a novel transcatheter mitral valve bioprosthesis.Four patients with severe mitral regurgitation, not eligible for mitral valve surgery, were treated with the CardiAQ valve. The procedures were performed under general anaesthesia, fluoroscopic and transesophageal echocardiographic guidance. We used a transapical approach in two patients and transseptal access in the others.Procedural success was obtained in all patients without extracorporeal circulation support. Mean procedure time was 128 min (range 90–180) and mean hospitalization duration was 12 days (range 4–24). The transseptal approach resulted in significantly shorter in-hospital stay with quick recovery. One patient died on day 35 from septicaemia and another one died after 5 months from major bleeding. The survival patients are presently in New York Heart Association I-II with improved left ventricular ejection fraction and normal quality of life.CardiAQ valve placement is safe using a transapical or transseptal approach. Following valve replacement, there was a marked functional improvement in survivors. Transcatheter mitral valve replacement is a promising therapy for mitral regurgitation in a selected patient population.