Objective To evaluate the accuracy of selected echocardiographic variables used to predict fluid responsiveness in hospitalized dogs with compromised hemodynamics and tissue hypoperfusion. Design Diagnostic test study in a prospective cohort of hospitalized dogs. Setting Veterinary referral clinics. Animals Forty-four hospitalized dogs with compromised hemodynamics and tissue hypoperfusion were utilized in this study. Interventions Echocardiographic examination before and after fluid replacement with 30 ml/kg of lactated Ringer's solution. Measurements and Main Results Pre-fluid replacement measurements of velocity of transmitral E wave (E-peak), the left ventricular end-diastolic internal diameter normalized to body weight (LVIDdN), and the left ventricular end-systolic internal diameter normalized to body weight (LVIDsN) were significantly lower in fluid-responsive patients compared with nonresponders (P < 0.001). The area under the receiver operating characteristic curve (AUROC) with its 95% confidence interval (CI) for each significant predictor was as follows: E-peak 0.907 (0.776-1.000, P < 0.001) and LVIDdN 0.919 (0.801-1.000, P < 0.001). The predictive capacity of LVIDsN was not significantly better than chance (AUROC, 0.753; 95% CI, 0.472-1.000, P = 0.078). A significant negative linear correlation was observed between the percentage of increase in velocity-time integral after expansion and the echocardiographic variables LVIDdN (r(s) = -0.452, P = 0.023) and E-peak (r(s) = -0.396, P = 0.008) pre-fluid replacement. The intraobserver and interobserver variability was very low (<5 %) for all measurements. Conclusions In this study using critically ill dogs with compromised hemodynamics and tissue hypoperfusion, pre-fluid replacement measurements of LVIDdN and E-peak adequately predict fluid responsiveness. Because a small number of fluid nonresponders were involved in the present study (11.4%), further studies that include larger numbers of fluid-nonresponsive animals are required.