Background: In spite of its expensiveness, two-dimensional echocardiogram (2D echo) is often overused as a screening tool for the exclusion of infective endocarditis (IE) in febrile patients with a low pretest probability of IE. The aim of this study was to evaluate the association of both Von Reyn criteria and 2D echo results with demographic variables, clinical findings, diagnosis of IE, and treatment change for targeting IE. Methods: Three hundred-two consecutive patients with fever referred to our institution for 2D echo indicating ���rule out IE��� were reviewed from January 1, 2005 to June 30, 2008. 2D echo was performed to confirm abnormal findings compatible with IE. Each episode was categorized by the Von Reyn criteria into probable/possible, or rejected based on clinical data available. Results: Two hundred sixty-three patients (87%) had fever. The mean age was 54 짹 17 years, and 60% were male. According to Von Reyn criteria, 273 patients were rejected group, and 29 patients were probable/possible group. In demographic characteristics according to von Reyn criteria, Probable/possible group was younger (48 years vs 55 years, P=.044), had more patients with fever (100% vs 86%, P=.020), with murmur (69% vs 8%, P<.001), with peripheral manifestation (14% vs 3%, P=.014), and with predisposing cardiac condition (59% vs 30%, P=.002) than rejected group. There were significant difference between Probable/possible group and rejected group in embolic events (55% vs 4%, P<.001), positive blood culture (90% vs 39%, P<.001), streptococcus viridans infection (65% vs 16%, P<.001), vegetation by 2D echo (76% vs 7%, P<.001), IE at discharge diagnosis (97% vs 7%, P<.001), and treatment for targeting IE after 2D echo (86% vs 9%, P<.001). Addition of 2D echo to Von Reyn criteria did not significantly contribute to change of treatment decision in rejected group (9% vs 7%, P=0.187). Conclusions: Most 2D echos are obtained in patients with a low pretest probability of IE and do not additionally contribute to treatment decision. 2D echo in the diagnosis and management of IE should be reserved for patients with intermediate or high probability of IE, based on clinical findings and positive blood culture results.