Introduction: Lung-protective ventilation strategy and prone positioning are the strategies practiced to manage patients suffering from acute respiratory distress syndrome (ARDS). Inferior Vena Cava Distensibility (dIVC) Index has been used for predicting fluid responsiveness (FR) in supine position. We conducted this study to observe the utility of dIVC in prone position in ARDS patients and compare it with esophageal Doppler (ED) parameters. Materials and Methods: After ethical clearance, a prospective observational pilot study was conducted in a 12-bedded tertiary care hospital. Adult ARDS patients who were treated with prone ventilation were included. Informed consent was taken from the relatives. IVC was visualized through right lateral approach both in supine and prone positions. We compared IVC distensibility and ED parameters, first in 45° head up and then in prone. FR was defined as an increase in the stroke volume of ≥15% as measured by ED. The patients with dIVC >18% were assumed to be fluid responsive. Statistical analysis was done using SPSS software version 20. Results: Twenty-five patients met the inclusion criteria. ARDS was (mean P/F ratio 116.64 ± 44.76) mostly due to pulmonary etiology. Out of 25 patients, 10 patients were fluid responsive based on dIVC (cutoff >18%) in supine position. When compared to ED values after passive leg raising, dIVC had a sensitivity and specificity of 77.78% and 81.25%, respectively, in predicting FR with a moderate-to-absolute agreement between the two methods. IVC distensibility showed statistically significant negative correlation with corrected flow time (FTc) values both in supine and in prone positions. Conclusion: IVC variability can be observed in acute respiratory distress syndrome patients in prone position. Inferior Vena Cava Distensibility correlates with flow time in both the positions.