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The growing need for less invasive therapies of cardiac disease creates the necessity for improved imaging guidance. Although two-dimensional transthoracic and transoesophageal echocardiography (TEE) have been shown to be essential tools for planning and execution of cardiac interventions, the benefit of three-dimensional TEE for the guidance of interventional procedures still needs to be evaluated. This review aims to describe our first experiences with real-time (RT) three-dimensional TEE for the guidance of percutaneous non-coronary interventions in the catheter laboratory. We used a matrix array TEE probe capable of generating three-dimensional images of cardiac structures in RT. We applied this innovative technique to monitor atrial septal defects or patent foramen ovale closures, valve procedures such as mitral and aortic valve interventions, and electrophysiological procedures. Our first experience using RT three-dimensional TEE for the guidance of percutaneous cardiac interventions in the catheter laboratory demonstrates that this technique is feasible to guide interventions, providing fast and complete information about the underlying pathomorphology, improving spatial orientation, and additionally allowing the online monitoring of the procedure. These benefits may accelerate the learning curve and improve confidence of the interventional cardiologist in order to increase safety, accuracy, and efficacy of interventional cardiac procedures.