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Objective: To evaluate the comparative diagnostic value of harmonic imaging (HI) in the assessment of patients with suspected infective endocarditis (IE). Setting: Tertiary referral centre. Design: 139 consecutive patients were evaluated with three imaging modalities: transthoracic echocardiography with fundamental imaging (FI); HI; and transoesophageal echocardiography (TOE). Image quality was assessed for each modality by semiquantitative scoring (0, poor, to 3, excellent). Presence, dimension, and characteristics of vegetations were assessed separately for each imaging modality, as well as presence of abscesses. Results: 35 patients had definite IE. TOE was positive in 33 patients, HI in 28, and FI in 12 (p <0.001 for FI vHI and vTOE). Mean image quality was 1 .4 (0.7) for FI, 2.1 (0.6) for HI (p < 0.01 vFI), and 2.6(0.4) for TOE (p <0.001 v HI). The association between FI and TOE findings was φ = 0.35 (x² = 17.57, p = 0.0014) and between HI and TOE it was (F = 0.95 (x² = 125.72, p < 0.0001; p <0.0001 v FI). The global echo score of vegetations was 7.1(3.3) with FI, 8.5 (3.4) with HI, and 11.3 (3.9) with TOE (p <0.001 v HI). Compared with TOE, FI identified only one of seven abscesses (sensitivity 14%) and HI identified two of seven abscesses (sensitivity 28%). Conclusions: HI provides an accurate assessment of suspected IE. TOE achieves superior definition of IE related abnormalities. [ABSTRACT FROM AUTHOR]