Objective: Fluid overload is an independent marker for mortality in critically ill patients. Assessment of fluid status and fluid responsiveness is crucial for the management of these patients. In this study, we compared the lactate level, inferior vena cava (IVC) diameter and non-invasive cardiac output (CO) monitoring in prediction of mortality in emergency department. Methods: This was a cross sectional observational study which comprised of 68 patients and was performed in ED of Tabriz University of Medical Sciences, Iran, from Sept 2016 until Sept 2017. IVC diameter was measured before the P-wave on ECG to avoid interference with a-wave and v-wave on the venous pressure curve, and during maximal inspiration and expiration to avoid Valsalva-like maneuvers. An arterial lactate sample was taken from all patients before performing the initial resuscitation. All patients underwent non-invasive CO monitoring by CO2 rebreathing technique. Mortality was noted on day 28. Results: Deceased patients had a significantly low level of IVC diameters, less CO values and more lactate levels. However, based on ROC curve analysis, the prediction accuracy and validity of both CO values obtained by rebreathing CO2 and IVC diameter was poor and the highest accuracy was obtained by lactate level assessment. Conclusion: Initial lactate value is a reliable parameter for prediction of mortality in non-traumatic critically ill patients. IVC diameter changes during spontaneous ventilation and non-invasive CO monitoring does not possess acceptable accuracy for prediction of mortality in these patients. doi: https://doi.org/10.12669/pjms.36.4.2032 How to cite this:Shahsavarinia K, Taqizadieh A, Moharramzadeh P, Amirchoupani R, Mahmoodpoor A. Comparison of cardiac output, IVC diameters and lactate levels in prediction of mortality in patients in emergency department; An observational study. Pak J Med Sci. 2020;36(4):---------. doi: https://doi.org/10.12669/pjms.36.4.2032 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.