Randomized clinical trials have shown that percutaneous closure of PFO with an occluder device in patients with a history of cryptogenic stroke reduces stroke recurrence compared to medical treatment alone. Recently, a fully different strategy implementing a suture-mediated percutaneous technique has been introduced in interventional practice with appealing advantages and promising results. We here provide an exhaustive overview of the principles and practice of suture-mediated PFO closure, highlighting the role of preprocedural imaging assessment to correctly identify its anatomical limitations and appropriately select patients who may mostly benefit from this newer and revolutionary approach.