Myocardial velocities have prognostic implications, and transmitral E wave to mitral annular early diastolic tissue velocity ratio (E/Em) is utilized to estimate left ventricular (LV) end-diastolic pressure (EDP). There are no reference values for 2-dimensional (2D) speckle tracking myocardial velocities (S2D, E2D, A2D), and it is unknown if they are comparable with color tissue Doppler imaging (TDI). Predictors of E/E2D ratios are unknown and E/E2D has not been validated with LVEDP. The myocardial velocities of 142 subjects were measured by TDI and 2D speckle tracking. Mean E/Em and E/E2D were calculated as transmitral E wave to mean 6 basal early diastolic myocardial velocities using TDI and 2D speckle tracking respectively, and compared with LVEDP during catheterizations (n = 20). Mean E2D was lower but mean S2D and A2D were higher than TDI (all p <0.001). When TDI sample volume was tracked throughout the cardiac cycle, this directional difference was no longer apparent with S2D, E2D, and A2D higher than TDI (all p <0.05). Age, systolic blood pressure, LV ejection fraction, and mean S2D were independent correlates of E/E2D. Receiver-operator characteristic analysis showed E/E2D (p = 0.03), not E/Em, identified elevated LVEDP (> or =12 mm Hg). E/E2D of 11.6 had 83% sensitivity and 70% specificity to predict elevated LVEDP. In conclusion, TDI and 2D speckle tracking myocardial velocities are not comparable due to angle independency and ability for tissue tracking with the latter. LV systolic function, age, and afterload are independent correlates of E/E2D. Only E/E2D identifies elevated LVEDP, and an E/E2D of 11.6 has the optimal sensitivity and specificity.