Systemic arterial hypotension is the only Food and Drug Administration approved indication for thrombolysis in patients with acute pulmonary embolism (PE). Recent guidelines suggest consideration of thrombolytic treatment in selected patients with haemodynamically stable PE, who have an intermediate risk for adverse outcome. Still, administration of thrombolytic therapy for hypoxia alone remains controversial. In this article we report a case of a patient with haemodynamically stable PE and a patent foramen ovale (PFO), requiring mechanical ventilation for hypoxaemic respiratory failure. We address the question whether the presence of a PFO in haemodynamically stable patients with acute PE could be an additional risk factor for an adverse outcome and an indication for thrombolysis. © 2012, Nederlandse Vereniging voor Intensive Care. All Rights Reserved.