OBJECTIVE To characterize the clinical course and outcomes of reported cases of splenic hemorrhage during thrombolytic or anticoagulant therapy. METHODS The Medline, EMBASE (Excerpta Medica), BIOSIS, and SCISEARCH databases for English and foreign literature between 1966 and 1991 were searched. All reports of patients with documented splenic hemorrhage during anticoagulant therapy or thrombolytic therapy were reviewed. Foreign language manuscripts were translated into English. RESULTS Seventeen cases of splenic hemorrhage associated with anticoagulant or thrombolytic therapy were found. In one case, there was minor antecedent trauma; in the remaining cases, hemorrhage was spontaneous. Mortality overall was 24% and was more likely in patients with splenic hemorrhage after thrombolytic therapy (50%) than in patients receiving long-term anticoagulants (9%). Splenectomy was performed in 12 of 13 survivors. CONCLUSIONS Splenic hemorrhage associated with anticoagulant or thrombolytic therapy is a rare entity. It may be lethal, especially when associated with lytic therapy. Reversal of the anticoagulated or lytic state and emergent splenectomy are the treatment of choice. Splenic hemorrhage can mimic acute myocardial infarction and cardiogenic shock and must be considered when the condition of cardiac patients receiving lytic or anticoagulant drugs suddenly deteriorates.