Accurate quantitative measurement of left ventricular (LV) ejection fraction (EF) by 2-dimensional echocardiography is limited by subjective visual endocardial border detection. Both harmonic and precision contrast microbubbles provide better delineation of endocardial borders than fundamental imaging. The aim of this study was to correlate 2-dimensional echocardiographic quantification of LVEF measured by 4 currently available techniques with radionuclide angiography. A total of 50 patients who underwent radionuclide (EF) measurement (47 of 50 had technically difficult echocardiograms by fundamental imaging) underwent echocardiography by 4 methods: fundamental alone, fundamental with contrast, harmonic alone, and harmonic with contrast. Three echocardiologists measured the biplane 2-dimensional echocardiographic LVEF independently and were blinded to radionuclide angiography. The correlation of echocardiographic EF with radionuclide EF improved incrementally with each method. However, contrast with harmonic imaging provided the closest correlation (r = 0.95, 0.96, and 0.95 as assessed by the 3 independent analysts.