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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 (rs = –0.452, P = 0.023) and E‐peak (rs = –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. [ABSTRACT FROM AUTHOR]