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Background: Majority of evidence concerning the prognostic significance of spontaneous echocardiographic contrast (SEC) was obtained before introduction and wide-spread use of harmonic imaging. It was established that harmonic mode greatly enhances the detection of SEC as compared with conventional fundamental imaging. It may be hypothesized that increased sensitivity may result in lower specificity and thus result in reduction or total abolishment of association between SEC and higher incidence of thromboembolic events as reported in the era of fundamental mode.Purpose: To investigate the prognostic value of SEC detected by transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) in the era of harmonic imaging.Methods: We retrospectively analyzed the database of tertiary cardiology centre echocardiographic laboratory and identified 60 patients with SEC (including 35 patients studied by TTE and 25 patients studied by TEE; patients with thrombi were excluded) and subsequently selected 60 sex- and age- matched controls without SEC. Data regarding baseline characteristics, treatment and clinical course during follow-up period (median: 33.5 months; 95% CI 24.79-40) were gained based on hospital and out-patient clinic documentation and telephone interviews. The clinical end-points included: all-cause death, cardiovascular death, stroke or transient ischemic attack (TIA), pulmonary embolism, peripheral embolism and composite thromboembolic end-point.Results: There were no significant differences in baseline clinical and demographic characteristics as well as in baseline echocardiographic characteristics between subjects with SEC and controls. We observed that SEC predicted higher mortality in whole study group (HR=7.41; p=0.0016) and in subgroup evaluated by TTE (HR=6.35; p=0.005). In the group assessed by TEE, SEC correlated with higher probability of stroke or TIA (p=0.04). By multivariate analysis, in all patients SEC was a predictor of cardiovascular death (OR=7.63; p=0.008) and its localization in the left atrium independently predisposed to thromboembolism (OR=10.15; p=0.012). Furthermore, left ventricular SEC detected by TTE also emerged as independent determinant of higher mortality (OR=5.26; p=0.015).Conclusions: Despite a lower threshold of detection using harmonic imaging SEC has still significant adverse prognostic implications, especially when observed on transthoracic examination.