We report an uncommon case of late infective endocarditis, in a patient with a history of intravenous drug abuse and HIV positivity, 9 years after a percutaneous closure of a patent foramen ovale. Despite a target and prolonged intravenous antibiotic therapy, he was then referred for surgical device and vegetation removal. Given the high risk associated with drug addiction lifestyle, especially in HIV positive cases, it is mandatory to observe this group of patients with lifelong follow-up and support. Furthermore, it may be considered a multidisciplinary-team approach to find the best option for these patients, also evaluating a surgical correction.