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An increasing number of patients are being evaluated for percutaneous patent foramen ovale (PFO) closure to prevent recurrent cerebrovascular events, but debate still exists on therapeutic indications and off-label closure device implantation. Pulmonary arteriovenous fistulas (PAVFs) are a rare and heterogeneous malformation prevalently associated with Rendu–Osler–Weber syndrome, and may mimic PFO right-to-left shunt (RLS), leading to unnecessary interventions and in some cases to relapses. Residual shunt is increasingly being observed both after PFO closure and PAVF embolization, even at long-term follow-up, with unclear clinical relevance. This instrumental and possibly therapeutic failure could lie in the presence of pulmonary microfistulas, either pre-existing or following the intervention. Hence, if RLS persists after optimal device placement and reasonable endothelialization time, the presence of a PAVF should be assumed and investigated; if RLS recurs after previous, negative echocontrast studies, presence of device-related complications or pulmonary microfistulas should be taken into consideration.