Respiratory variability of peak velocities (RVPV) in the common femoral vein measured with ultrasound can reveal venous outflow obstruction. Pulse wave (PW) Doppler is the gold standard for venous velocity estimation of the lower extremities. PW Doppler measurements are angle dependent, whereas vector flow imaging (VFI) can yield angle-independent measures. The hypothesis of the present study was that VFI can provide RVPV estimations without the angle dependency of PW Doppler for an improved venous disease assessment. Sixty-seven patients with symptomatic chronic venous disease were included in the study. On average, VFI measured a lower RVPV than PW Doppler (VFI: 14.11 cm/s; PW: 17.32cm/s, p = 0.002) with a non-significant improved precision compared with PW Doppler (VFI: 21.09%; PW: 26.49%, p = 0.08). In a flow phantom, VFI had improved accuracy (p < 0.01) and equal precision compared with PW Doppler. The study indicated that VFI can characterize the hemodynamic fluctuations in the common femoral vein.