We report the first human case of percutaneous transcatheter mitral valve repair with the MitraClip system under conscious sedation in a patient with severe mitral regurgitation. The procedure was performed using the standard MitraClip technique, in the catheterization laboratory, with transesophageal echocardiographic and fluoroscopic guidance. Transesophageal echocardiography is the primary imaging modality of the MitraClip procedure, which usually necessitates general anesthesia to guarantee complete immobilization of the patient allowing precise delivery of the MitraClip device. We successfully performed the procedure under deep sedation, using remifentanil and local anesthesia in a patient who had serious contraindications to general anesthesia. The success of this procedure suggests that percutaneous transcatheter mitral repair with the MitraClip system can be safely realized using conscious sedation. Conscious sedation may represent a convenient alternative approach for selected patients who undergo this innovative procedure.