Local pressure differences estimated using vector flow imaging (VFI) and direct catheterization in seven carotid bifurcation phantoms were compared with simulated pressure fields. VFI correlated strongly with simulated peak pressure differences (r = 0.99, p < 0.00001), with an average overestimation of 12.3 Pa (28.6%). The range between the lowest and highest pressure difference of VFI underestimated simulations by 4.6 Pa (8.06%; r = 0.99, p < 0.0001). The catheter method exhibited no correlation (r = –0.09, p = 0.85). Ten repeated measurements on one phantom revealed a small standard deviation (SD) for VFI (SD = 8.4%, mean estimated SD = 11.5%), but not for the catheter method (SD = 785.6%). An in vivo peak systolic pressure difference of 97.9 Pa (estimated SD = 30%) was measured using VFI in one healthy individual. This study indicates that VFI pressure difference estimation is feasible in phantoms and in vivo and realistic estimates of the SD can be attained from the data.