To our knowledge, we describe the first reported case of paradoxical embolization via a patent foramen ovale (PFO) in an adult with moderately severe cystic fibrosis (CF) and advanced lung disease. Fluctuating neurologic symptoms and signs suggestive of cerebrovascular disease in an adult patient with advanced CF may be due to paradoxical embolization via a PFO. The possibility of a PFO should be considered before placement of a totally implantable venous access device to avert unnecessary risk of stroke in CF patients. Further study is needed to determine whether the use of a totally implantable venous access device increases the risk of paradoxical embolization in adult CF patients with a PFO.