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Rationale: Peripheral artery disease (PAD) is common among the elderly and increases the risk of cardiovascular events, disability and death. PAD course and outcomes depend not only on the condition of macrovasculature but also on the tissue perfusion. We have previously shown that Type 2 diabetic patients with lower extremity ischemia have significantly lower perfusion than healthy volunteers, and the ratio of basal perfusion in the arm and leg (BP1/BP3) measured by incoherent optical fluctuation flowmetry (IOFF) allows to identify hemodynamically significant stenoses. Aim: To analyze associations between perfusion parameters registered by IOFF and the severity of vascular involvement in PAD patients. Methods: This single center cross-sectional study included 38 PAD patients admitted to the Department of Vascular Surgery and Coronary Artery Disease. The arteries were assessed with duplex Doppler ultrasonography (DDU), according to the results of which the PAD severity score and ankle-brachial index (ABI) were calculated. Skin microhemodynamic parameters were recorded by IOFF. The basal perfusion on the arm (BP1), the dorsal foot surface and the toe (BP2 and BP3), the ratio BP1/BP3, local thermal hyperemia (LTH2 and LTH3) and an increase in perfusion after heating on two leg zones (LTH2-BP2, LTH3-BP3) were evaluated and expressed in perfusion units (PU). BP1, BP3, and BP1/BP3 values were additionally measured with laser Doppler flowmetry (LDF). The analysis was performed depending on the degree of arterial involvement determined by DDU for each limb separately (n = 73). There were ≥ 50% stenoses in 15 extremities (Group 1), occlusion of one of the major arteries in 42 (Group 2) and ≥ 2 occlusions in 16 lower extremities (Group 3). Results: In the groups 1, 2 and 3, the values of most parameters estimated by IOFF decreased with an increase in severity of limb lesions. As an example, the respective perfusion parameters for the big toe in the study groups were as follows: BP3 4.0 [2.0; 9.8], 2.2 [0.9; 3.7] and 1.1 [0.7; 2.6] PU (p = 0.007); LTH3 10.0 [6.4; 14.9], 5.0 [1.5; 7.8] and 2.5 [1.4; 4.5] PU (p 0.001), and LTH3-BP3 3.8 [2.6; 7.8], 2.4 [0.6; 4.3] and 1.2 [0.4; 1.5] PU (p = 0.001). The BP1/BP3 ratio in the above mentioned group increased: 1.8 [0.8; 7.7], 7.2 [3.4; 21.3] and 14.2 [6.6; 18.3] (p = 0.004), respectively. No similar trend was found for this parameter registered by LDF. There were significant correlations between the lower extremities perfusion parameters measured by IOFF and ABI, with the correlation coefficients ranging from 0.365 to 0.717 (p 0.05). Conclusion: The functional parameters of the skin microhemodynamics vary with different PAD severity. In addition, they correlate with clinical indicators of atherosclerosis. The IOFF technique can be promising as an additional quantitative method for assessment of microvascular blood flow in patients with PAD.