The management of acute submassive pulmonary embolism is undertaken on an individualized basis because of the wide spectrum of clinical presentations. In this report we review the literature and discuss the evidence behind the management of cases of acute pulmonary embolism complicated by hypoxemia from a patent foramen ovale. In a case of acute pulmonary embolism complicated by refractory hypoxemia from an intracardiac shunt, adjunctive therapies in addition to anticoagulation and thrombolysis must be considered.