Introduction: Identification of occult hypovolemia in trauma patients at admission can be difficult without additional laboratory evaluation or advanced imaging. We hypothesized that in acute trauma patients, the response of ultrasound-measured minimum inferior vena cava diameter (IVCD MIN ), IVC Collapsibility Index (IVCCI) or minimum internal jugular diameter (IJVD MIN ) or IJV Collapsibility Index (IJVCI) in repeated ultrasound examinations (USA-IVC) during up to 1 hour of standard-of-care intravenous fluid resuscitation would predict 24hour resuscitation intravenous fluid requirements (24FR). Methods: An NTI funded, AAST-MITC group prospective, multi-institutional cohort trial was conducted at 4 Level I Trauma Centers. Major trauma patients were screened in the supine position for an IVCD of 12 mm or IVCCI of 50% or less on the initial FAST examination for enrollment. A second IVCD was obtained 40-60 minutes later, after the patient received standard-of-care fluid resuscitation. Patients whose second measurement IVCD was less than 10mm were deemed Non-Responders (NON-RESP), those at or greater than 10mm were Responders (RESP). Prehospital fluid, initial resuscitation fluid and 24FR were recorded. Demographics, ISS, arterial blood gasses, ICU admission, length-of-stay, interventions and complications were recorded. Means were compared by ANOVA and categorical variables were compared via Chi-square. Receiver-operator characteristic (ROC) curves and gray area analysis were used to compare the IVC and IJV measures and to Base Excess (BE), ISS and other 24FR predictors.Results: There were 4798 patients screened by FAST-IVC, 196 were identified with admission IVCD of 12 mm or IVCCI of 50% or less, 144 were enrolled and had useable Abstract imagery. After 1 hour of standard of care resuscitation, there were 86 RESP and 58 NON-RESP. There were no significant differences between groups in demographics. initial hemodynamics or laboratory measures. NON-RESP had smaller IVCD (6.0mm ± 3.7 vs.14.2mm ± 4.3, p< 0.001) and higher IVCCI 41.7% ± 30.0 vs. 13.2% ± 12.7, p< 0.001) but no significant difference in IJVD or IJVCCI. RESP had significantly greater 24FR than NON-RESP (2503ml ± 1751 vs. 1243ml ± 1130 0.003). ROC analysis indicates IVCD MIN predicted 24FR (AUC= 0.74, C.I.: 0.64-0.84, p<0.001) as did IVCCI (AUC= 0.75, C.I.: 0.65-0.85, p<0.001) not IJVD (AUC= 0.48, C.I.: 0.24-0.60, p=N.S.) or IVCCI (AUC= 0.54, C.I.: 0.42-0.67, p=N.S.) and more predictive than ISS (AUC=0.65, C.I.:0.54-0.76, p=0.007) in predicting 24FR. Conclusion: Ultrasound assessed IVCD MIN and IVCCI but not IJ diameter response to initial major trauma patient resuscitation predicts 24-hour fluid resuscitation requirements.