Paravalvular leaks (PVLs) represent a challenging complication following surgical mitral valve replacement, particularly in patients with connective tissue disorders such as Marfan syndrome. This report presents the case of a 32-year-old female with Marfan syndrome who presented with progressive dyspnea and New York Heart Association (NYHA) functional class II-III symptoms 10 years post-mitral valve replacement for severe mitral regurgitation. Transthoracic and transesophageal echocardiography identified an 8 × 9 mm paravalvular defect with compliant borders, deemed suitable for percutaneous closure. Surgical re-intervention was considered high risk by the Heart Team, leading to the decision to proceed with a minimally invasive approach. Under general anesthesia, the defect was crossed using a steerable guide catheter and stabilized with a super-stiff wire. A stepwise closure strategy employing three Amplatzer Vascular Plug III devices (two 14 × 5 mm and one 10 × 5 mm) successfully reduced the regurgitation to trace levels. The patient experienced significant symptomatic improvement, achieving NYHA functional class I at six months post-procedure, with echocardiography confirming the durable closure of the defect. This case highlights the technical nuances and innovative use of multiple devices for mitral PVL closure, particularly in the context of connective tissue disorders. Multimodality imaging, strategic device selection, and operator expertise are critical for optimizing outcomes in such high-risk scenarios.