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Background and Objectives: This study aimed to evaluate the utility and accuracy of dual-energy automatic plaque removal (DE-APR) in patients with symptomatic peripheral arterial disease (PAD) using digital subtraction angiography (DSA) as the reference standard. Materials and Methods: We retrospectively analyzed 100 patients with PAD who underwent DE computed tomography angiography (DE-CTA) and DSA of the lower extremities. DE-CTA was used to generate APR subtracted images. In the three main arterial segments (aorto-iliac segment, femoro-popliteal segment, and below-the-knee segment), the presence or absence of hemodynamically significant stenosis (>50%) and calcification was assessed using the images. CTA data were analyzed using different imaging approaches (DE-standard reconstruction image (DE-SR), DE-APR maximum intensity projection image (APR), and DE-SR with APR). Results: For all segments evaluated, the sensitivity, specificity, and accuracy for detecting significant stenosis were 98.16%, 81.01%, and 89.58%, respectively, with DE-SR; 97.79%, 83.33%, and 90.56%, respectively, with APR; and 98.16%, 92.25%, and 95.20%, respectively, with DE-SR with APR. DE-SR with APR had greater accuracy than DE-SR or APR alone (p < 0.001 and p < 0.001, respectively). When analyzed based on vascular wall calcification, the accuracy of DE-SR with APR remained greater than 90% regardless of calcification severity, whereas DE-SR showed a considerable reduction in accuracy in moderate to severe calcification. In the case of APR, the degree of vascular wall calcification did not significantly influence the accuracy in the aorto-iliac and femoro-popliteal segments. DE-SR with APR achieved significantly higher diagnostic accuracy for all lower extremity segments in evaluating hemodynamically significant stenosis in patients with symptomatic PAD and transcended the impact of vascular wall calcification compared with DE-SR. Conclusions: APR demonstrated favorable diagnostic performance in the aorto-iliac and femoro-popliteal segments, exhibiting good agreement with DSA even in cases of moderate to severe vascular wall calcification.