The role of transcatheter mitral valve repair with MitraClip implantation is becoming increasingly important for high-risk surgical patients with significant mitral regurgitation. Eligibility criteria for MitraClip are however rather strict, and the risk–benefit balance of this device in off-label settings remains unclear. Patients with prior heart transplantation may represent particularly challenging candidates for MitraClip, given their peculiar atrial anatomy. We hereby present the case of a 72-year-old gentleman with prior heart transplantation and significant mitral regurgitation who, after heart team consensus, was referred to us for MitraClip implantation. After careful planning, we were able to successfully implant two clips, achieving a significant improvement in the severity of the mitral regurgitation. Similarly favorable findings were confirmed at 3-month clinical and transthoracic/transesophageal echocardiographic follow-up. This clinical vignette highlights the key procedural milestones for successfully implanting MitraClip in patients with significant mitral regurgitation and prior heart transplantation.