Pulmonary embolism (PE) remains one of the highest causes of cardiovascular mortality worldwide. Systemic thrombolysis for acute PE reduces cardiovascular collapse but has the potential to cause major complications, including intracranial hemorrhage, systemic hemorrhage, immunologic complications, hypotension, and myocardial rupture. Catheter-directed thrombolysis accompanied with high-frequency ultrasound reduces systemic dose, allows increased local dose, and expedites clot lysis at the site of embolism. Although rare, some patients may have a patent foramen ovale or other atrial septal defect (ASD) which cannot be visualized during fluoroscopy which may complicate this procedure. A 41-year-old diabetic smoker presented to the emergency department with hypoxia, tachycardia, and light headedness. Computed tomography angiography (CTA) of the chest revealed bilateral PE with right ventricular enlargement and right heart strain pattern. Transthoracic echocardiogram revealed right ventricular enlargement. He was diagnosed with submassive PE. He underwent right heart catheterization with two angled pigtail catheters manipulated through the right heart to reach the right and left pulmonary arteries, however on frontal fluoroscopy, the catheters appeared slightly more caudal than would be expected. Lateral fluoroscopy was performed which did not show the catheter going through the expected anterior curvilinear course of the right ventricle and pulmonary trunk. Contrast was injected into each pigtail catheter and this demonstrated retrograde flow of contrast back into the left atrium, confirming that the catheters were positioned in the pulmonary veins, having passed through an ASD. On review of CTA chest, there was a visible patent foramen ovale. Congenital heart defects are rare but can complicate certain procedures and interventionalists need to be aware of this possibility. Catheter position more caudal than the pulmonary artery silhouettes should alert the operator to the incorrect placement in the pulmonary veins through an ASD. In these circumstances, lateral fluoroscopy will show absence of the catheters along the expected anterior curvilinear route of the right ventricle, pulmonary infundibulum, and pulmonary trunk. Contrast injection will show centripetal flow back to the left atrium rather than the centrifugal flow away from the heart. Other potential confirmatory methods include pressure monitoring and blood gas sampling. In addition, careful scrutiny of the CT angiogram for an ASD before the procedure may alert the operator to this potential pitfall. The interventionalist must remain vigilant to unexpected anatomical variants to avoid potential harm.