Introduction: Nontraumatic undifferentiated hypotension is one of the common and challenging critical presentations in the emergency department (ED) due to the difficulty in diagnosing the etiology of shock. In the present study, an attempt was made to test point-of-care ultrasound (PoCUS) as an early approach to improve the accuracy of diagnosis and to narrow the differentials in cases of nontraumatic undifferentiated hypotension. Materials and methods: This is a prospective explorative study conducted in the ED of a tertiary care hospital over a period of 18 months. A total of 100 patients were included in the study. All patients >18 years of age with systolic blood pressure <90 mm Hg with at least one sign or symptom of hypoperfusion were included in the study. Patients referred from another hospital as shock, history of trauma, and history suggestive of orthostatic hypotension and presented with symptomatic postural hypotension as the only chief complaint were excluded. All the patients who met the inclusion/exclusion criteria underwent detailed clinical and multi-organ PoCUS evaluation by two different observers. Assessment of the lungs, cardia, abdomen, aorta, inferior vena cava (IVC), and leg veins during the PoCUS examination was done. A third observer combined the clinical evaluation and the PoCUS findings. All patients were followed through for their final diagnosis at the time of discharge. First, the diagnosis after clinical evaluation alone was compared to the final diagnosis. Then the diagnoses based on the findings of PoCUS alone were compared with the final diagnosis. Last, the diagnosis obtained on combining the data of clinical evaluation with that of PoCUS was compared to the final diagnosis. The data were analyzed based on their reliability indices, accuracy, and the Cohen's kappa coefficient. Results: Diagnoses based on clinical evaluation alone and POCUS alone were found to be accurate in 45% and 47% of patients, respectively. But on combining the findings of clinical evaluation with PoCUS, the accuracy increased to 89%. The most common etiology of shock was found to be distributive shock present in 38% of patients with sepsis being the most common subtype. In patients with obstructive shock, combined clinical evaluation with PoCUS was in perfect agreement with Cohen's kappa coefficient (κ) = 1 and those with distributive shock were in substantial agreement with Cohen's kappa coefficient (κ) = 0717. The overall kappa correlation of the combined evaluation with PoCUS was 0.89, which shows an almost perfect agreement with the final diagnosis. Conclusion: This study demonstrates the accuracy and reliability of PoCUS as an easy and valuable bedside tool when added to the clinical evaluation. It helps in narrowing the differentials and thereby guiding early goal-directed therapy in nontraumatic, undifferentiated hypotension patients presenting to the ED.