The risk of pulmonary embolism is substantial in patients hospitalized for major bleeding, especially when intracranial. Conversely, management of pulmonary embolism can be complicated by bleeding and the risk for bleeding may be greater the more extensive the embolism. Various clinical prediction rules for such bleeding complications have been studied and will be reviewed here. Also discussed in this chapter is the use of a prediction rule that should lead to a modification of treatment with an anticoagulant or fibrinolytic agent, which is also discussed here. In case bleeding occurs, there is a difficult balance between controlling the hemorrhage and treating the pulmonary embolism. Several scenarios, depending on severity of each of the two events and the timing, are possible, and the management will vary accordingly. Nevertheless, the prognosis for patients with pulmonary embolism complicated by major hemorrhage is often dismal since there might be ominous contributing risk factors.