Background Transpulmonary passage of air emboli can lead to fatal brain‐ and myocardial infarctions. We studied whether pigs with open chest and pericardium had a greater transpulmonary passage of venous air emboli than pigs with closed thorax. Methods We allocated pigs with verified closed foramen ovale to venous air infusion with either open chest with sternotomy and opening of the pleura and pericardium (n = 8) or closed thorax (n = 16). All pigs received a five‐hour intravenous infusion of ambient air, starting at 4‐6 mL/kg/h and increased by 2 mL/kg/h each hour. We assessed transpulmonary air passage by transesophageal M‐mode echocardiography and present the results as median with inter‐quartile range (IQR). Results Transpulmonary air passage occurred in all pigs with open chest and pericardium and in nine pigs with closed thorax (56%). Compared to pigs with closed thorax, pigs with open chest and pericardium had a shorter to air passage (10 minutes (5‐16) vs. 120 minutes (44‐212), P < .0001), a smaller volume of infused air at the time of transpulmonary passage (12 mL (10‐23) vs.170 mL (107‐494), P < .0001), shorter time to death (122 minutes (48‐185) vs 263 minutes (248‐300, P = .0005) and a smaller volume of infused air at the time of death (264 mL (53‐466) vs 727 mL (564‐968), P = .001). In pigs with open chest and, infused air and time to death correlated strongly (r = 0.95, P = .001). Conclusion Open chest and pericardium facilitated the transpulmonary passage of intravenously infused air in pigs.