Objective: To investigate the feasibility of developing an animal model of patent foramen ovale (PFO) in piglets by percutaneous atrial septal puncture and balloon dilation. Methods: A standardized percutaneous atrial trans-septal puncture and balloon dilation was conducted in 11 healthy piglets under general anesthesia. A Rups-100 system inserted through a femoral vein was used for the transseptal puncture, and subsequent balloon dilatation was performed at the puncture site to imitate a PFO. Euthanasia and autopsy were performed on day 1 in one piglet (early autopsy), and on day 21 in the remaining ten piglets (late autopsy). Results: Artificial PFO was successfully created in all piglets and verified by fluoroscopy. No major technical difficulty or complication was encountered except in one which developed mild hemopericardium. In the piglet that had early autopsy, the artificial foramen was measured 0.860.7 cm(2) in cross-section and aggregates of erythrocytes were revealed over its rim under light microscopy. In the late autopsy group (n=10), seven piglets had the created foramens healed and sealed off, while the other three showed relatively small residual lumens measured 0.1x0.2 cm(2), 0.2x0.2 cm(2) and 0.1x0.3 cm(2) in cross-section, respectively. Histological examination of specimens from the late autopsy group showed variable neointima hyperplasia, cardiac muscle necrosis and focal fibrosis at the puncture site, regardless of the course of healing. Conclusion: Artificial creation of PFO in piglets is feasible by percutaneous atrial septal puncture and balloon dilation. This protocol may serve as a research model for PFO-related stroke in human.