Our experience at the Cleveland Clinic and that in the literature with splenic infarction were reviewed to describe the natural history of splenic infarction and provide guidelines for management. Data for this review included 75 patients identified by clinical studies or at autopsy during a 10-year period and a review of 77 cases reported in the literature. The cause of the infarct varied with age; patients under 40 years old most often had an associated hematologic disorder, while those older than 41 years old most often had an embolic event. Other etiologic factors included splenic vascular disease, anatomic abnormalities, collagen vascular disease, pancreatic disease, and nonhematologic malignancy. Left upper quadrant pain was the predominant symptom. Changes in the blood count included anemia (53%), leukocytosis (49%), and thrombocytosis (7%). Liver-spleen scans were diagnostic in 90% of patients and computerized tomography identified the infarct in 75%. Initial management consisted of hydration, analgesics, and frequent monitoring, with resolution of symptoms in 7 to 14 days. Splenectomy was performed for persistent symptoms or a complication of the infarct (splenic pseudocyst, abscess, or hemorrhage). An uncomplicated splenic infarction can be managed safely with medical treatment, but early surgical intervention (splenectomy) is necessary to lower the mortality rate of a complication of the infarct.