Introduction: Measurement of local hemodynamic behavior is useful for assessing the pathology of carotid stenosis. In this study, we explore a novel method using two-dimensional digital subtraction angiography (2D DSA) to provide time-dependent pressure data. We performed comparative validation with computational fluid dynamics (CFD) and flow guidewire measurements as reference methods. Methods: A silicone phantom model of a carotid stenosis was prepared, filled with physiological saline, and connected to a flow pump (Vascular Simulations, LLC Left Heart Replicator) applying pulsatile flow. The stenosis model narrowed from a diameter of 1.37 cm to 0.58 cm for a length of 0.64 cm (NASCET=40%). Iodinated contrast media was injected, and time dependent pressure profiles at four regions of interest: 2 cm proximal to the stenosis, proximal end of the stenosis, distal end of the stenosis and 2 cm distal to the stenosis were derived from contrast intensity (I) obtained from 2D DSA background-subtracted intensity plots using previously published PVEC software. A Volcano flow guidewire sensor was utilized at the same four locations to collect flow data. Pulsatile CFD flow analysis was performed to extract flow data. Results: DSA PVEC contrast analysis allowed observation of distinct flow pulsatility. At 30fps, strong agreement of DSA contrast waveform matching CFD and guidewire flow measurements was found at the distal end of the stenosis over a period of linear contrast increase (constant dI/dt). Bland-Altman analysis was used to compare derived pressure with the reference methods over 3.5 cardiac cycles, from 5.9 s to 8.7 s after the initial injection of contrast. 2D DSA-derived pressure showed a mean departure of -10.24% (std. dev 14.65%) pressure obtained from CFD analysis, and a mean departure of -15.32% (std. dev 14.24%) from guidewire measurements for the duration. Conclusion: A novel computational approach suggests 2D DSA can provide real-time results to approximate carotid flow from 2D DSA. We showed using this novel approach the flow data is comparable with guide wire and CFD methods. Future experiments may allow it to provide a supplementary, non-invasive means to examine local hemodynamic behavior that is relevant to the evaluation of carotid stenosis.