The maximum value of the first derivative of the invasively measured left ventricular (LV) pressure (+ dP/dtmax or P′) is often used to quantify LV contractility, which in mice is limited to a single terminal study. Thus, determination of P′ in mouse longitudinal/serial studies requires a group of mice at each desired time point resulting in “pseudo” serial measurements. Alternatively, a noninvasive surrogate for P′ will allow for repeated measurements on the same group of mice, thereby minimizing physiological variability and requiring fewer animals. In this study we evaluated aortic acceleration and other parameters of aortic flow velocity as noninvasive indices of LV contractility in mice. We simultaneously measured LV pressure invasively with an intravascular pressure catheter and aortic flow velocity noninvasively with a pulsed Doppler probe in mice, at baseline and after the administration of the positive inotrope, dobutamine. Regression analysis of P′ versus peak aortic velocity (vp), peak velocity squared/rise time (vp2/T), peak (+ dvp/dt or v′p) and mean (+ dvm/dt or v′m) aortic acceleration showed a high degree of association (P′ versus: vp, r2 = 0.77; vp2/T, r2 = 0.86; v′p, r2 = 0.80; and v′m, r2 = 0.89). The results suggest that mean or peak aortic acceleration or the other parameters may be used as a noninvasive index of LV contractility.