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Measurement of inferior vena cava collapsibility (cIVC) by point-of-care ultrasound (POCUS) has been proposed as a viable, non-invasive means of assessing fluid responsiveness. We aimed to determine the ability of cIVC to identify patients who will respond to additional intravenous fluid (IVF) administration among spontaneously breathing critically-ill patients.Prospective observational trial of spontaneously breathing critically-ill patients. cIVC was obtained 3 cm caudal from the right atrium and IVC junction using POCUS. Fluid responsiveness was defined as a ≥ 10% increase in cardiac index following a 500 ml IVF bolus; measured using bioreactance (NICOM™, Cheetah Medical). cIVC was compared with fluid responsiveness and a cIVC optimal value was identified.Of the 124 participants, 49% were fluid responders. cIVC was able to detect fluid responsiveness: AUC = 0.84 [0.76, 0.91]. The optimum cutoff point for cIVC was identified as 25% (LR + 4.56 [2.72, 7.66], LR- 0.16 [0.08, 0.31]). A cIVC of 25% produced a lower misclassification rate (16.1%) for determining fluid responsiveness than the previous suggested cutoff values of 40% (34.7%).IVC collapsibility, as measured by POCUS, performs well in distinguishing fluid responders from non-responders, and may be used to guide IVF resuscitation among spontaneously breathing critically-ill patients.IVC collapsibility, as measured by POCUS, is able to detect fluid responsiveness.Use of a passive leg raise did not improve detection of fluid responsiveness.The optimum cutoff point for IVC collapsibility is cIVC = 25%.cIVC, measured by POCUS may be used to direct fluid resuscitation.