© 2020 American Institute of Ultrasound in MedicineObjectives: This prospective study was performed to evaluate the diagnostic role of point-of-care lung ultrasound (LUS) and inferior vena cava (IVC) ultrasound in patients with acute decompensated heart failure (ADHF). Methods: A prospective cohort study was conducted between January 2018 and November 2018 on patients with a diagnosis of ADHF in the emergency department (ED). On admission, LUS findings, inspiratory and expiratory IVC diameters, and the inferior vena cava collapsibility index (IVCCI) were obtained. After therapeutic interventions, third-hour changes in LUS and the IVC index and the treatment response were assessed. Results: Eighty patients were enrolled. Forty-six (58%) patients had an ejection fraction (EF) greater than 40%, and 34 (42%) had an EF of less than 40%. Significant differences were detected between the admission and third-hour inspiratory IVC diameter, expiratory IVC diameter, and IVCCI (P =.001). There was no correlation between the EF and inspiratory IVC diameter (r = −0.03; P =.976), expiratory IVC diameter (r = −109; P =.336), or IVCCI (r = −0.72; P =.523) and between the B-type natriuretic peptide level and inspiratory IVC diameter (r = −0.58; P =.610), expiratory IVC diameter (r = −0.33; P =.774), or IVCCI (r = −0.78; P =.493) either. A comparison of admission and third-hour numbers of B-lines on LUS imaging showed a significant decrease in the number of B-lines in all zones at the end of 3 hours (P =.001). A significant difference existed between the hospitalized and discharged patients with respect to IVC diameters and number of B-lines. Conclusions: In the ED setting, an assessment of B-lines and measurement of IVC diameters are better markers than the B-type natriuretic peptide level, EF, or chest x-ray for diagnosis of ADHF and can be used to make decisions for hospitalization or discharge from the ED.