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Background Patients with a very low probability of infective endocarditis (IE) do not benefit from transthoracic echocardiography (TTE). Because the term ‘very low probability' has not yet been defined, the present prospective study sought to identify the population with a ‘very low probability'. Methods TTE was performed between July 2005 and October 2006 in consecutive patients clinically suspected of having IE. Clinical parameters suggestive of IE and presence of infectious focus were recorded. Results Twenty-four (15.5%) of 155 patients studied had positive findings on TTE. Significant positive predictors were embolic events, intravenous drug use, the presence of a prosthetic valve, positive blood cultures and immunological phenomena. The significant negative predictor was confirmed infection sites other than endocardium. Sixty-three (40.6%) of 155 patients without positive predictors were found to have no vegetation. Thus, the collective absence of these predictors indicated a zero probability of TTE showing evidence of IE. A significant negative predictor was a definite etiology of infection other than IE. Only one in 76 patients was diagnosed with both IE and infection at another site. Conclusions The absence of positive predictors or the presence of a negative predictor indicate a near-zero probability of IE being detected by TTE. Use of clinical parameters may avoid up to 41% of unnecessary TTE examinations, increasing the likelihood that such a diagnosis will be correct.