Background: Elastic compression therapy (CT) in patients with peripheral artery disease (PAD) and chronic venous insufficiency (CVI) may compromise arterial perfusion. We evaluated the feasibility of a toe-flexion test, which quantifies dynamic foot perfusion by near-infrared spectroscopy (NIRS), for the assessment of hemodynamic sustainability of CT in PAD patients with CVI. Patients and methods: In this prospective observational study, PAD patients aged 50–85 with combined CVI at CEAP stages II–IV were studied. The ankle-brachial index (ABI) was measured, and foot perfusion was determined after 10 consecutive toe-flexion movements with NIRS sensors placed on the dorsum of each foot. Knee-high open-toe compression stockings were applied, and the degree of compression was measured. Toflex-area was determined by calculating the area under the curve of the oxygenated hemoglobin track recorded by NIRS. A toflex-area reduction > 20 % following CT was arbitrarily defined to identify limbs of patients with improved foot perfusion. These subjects received CT to be worn and a diary to report adherence and symptoms. Results: Forty-seven PAD patients (74 ± 9 years; ABI 0.67 ± 0.24) with CVI were enrolled. For all legs, superimposable toflex-areas were observed for the first two attempts (ICC 0.92). Following application of CT (17 ± 2 mmHg), the toflex-area improved (from –162 ± 110 a.u. to –112 ± 104 a.u.; p < .001). Sixty-two limbs (n = 32 patients) exhibited improved foot perfusion after CT, with a mean variation of 80 ± 47 a.u., while 32 limbs (n = 23 patients) showed stable or worsened values. In a regression model, favorable variations in toflex-area after CT were linked to a worse baseline toflex-area (R2 = 0.18; p < 0.001; rpartial = –0.42) while the percentage improvement directly correlated with CEAP class (p = 0.033). Conclusions: The NIRS-assisted test, which is feasible in a laboratory context, objectively discriminates the hemodynamic tolerability of the treatment and identifies subjects with combined PAD and CVI with improved perfusion after CT, in spite of the presence of PAD.