Background This study explores the comparison between Doppler ultrasound and multidetector CT angiography (MDCTA) in diagnosing peripheral arterial disease (PAD), emphasizing the urgent need for precise and minimally invasive methodologies in vascular medicine. PAD, stemming from atherosclerosis, manifests as reduced blood flow and symptoms, such as claudication, requiring timely and accurate diagnosis for optimal treatment outcomes. Doppler ultrasound emerges as an option, offering a non-invasive and cost-effective approach. Conversely, MDCTA provides intricate images, albeit with associated risks, such as radiation exposure and potential complications from contrast agents. This research rigorously evaluates the efficacy, safety, and cost-efficiency of these modalities, aiming to provide clinicians with valuable insights for informed decision-making, ultimately enhancing standards of patient care. Methodology In this prospective study conducted at Saveetha Medical College, Chennai, 34 patients diagnosed with PAD were enrolled to compare the efficacy of duplex ultrasound and MDCTA in identifying arterial lesions. Statistical analysis comprised kappa statistics and contingency tables to evaluate the concordance between the modalities, with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) being calculated. Exclusions were made for patients with contraindications to MDCTA, those under 18 years of age, severe renal impairment, and allergies to contrast agents. This research examined the diagnostic accuracy of both imaging techniques, aiming to provide valuable insights into their effectiveness in identifying arterial lesions associated with PAD. Statistical analysis This investigation studied the efficacy of Doppler ultrasound and MDCTA in diagnosing PAD, with a particular focus on comparing the accuracy of Doppler ultrasonography (DUS) against MDCTA using sensitivity, specificity, and Cohen's kappa coefficient. Through segmental analysis, valuable insights were garnered into the diagnostic precision of DUS across various arterial segments. The results underscored the significance of DUS as a safe, cost-effective, and non-invasive alternative that complements the utility of MDCTA. This comprehensive assessment sheds light on the comparative strengths of both modalities, offering invaluable guidance for clinicians in selecting optimal diagnostic approaches for PAD assessment. Statistical analysis was conducted using the Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 24.0, Armonk, NY). Results The sensitivity of ultrasonography (USG) arterial Doppler in evaluating the supra-inguinal, femoropopliteal segments, and infrapopliteal segments was 87.5%, 100%, and 75.32%, respectively. The specificity in evaluating supra-inguinal, femoropopliteal segments, and infrapopliteal segments was 100%, 96.01%, and 83.06%, respectively. The agreement between the two modalities (USG arterial Doppler and CT angiography) obtained by Cohen's kappa analysis with respect to the aortoiliac region and femoropopliteal region was very good (0.91). For infrapopliteal vessels, it was only moderate (0.76). Conclusion Duplex ultrasound emerges as an indispensable tool in the investigation of PAD, offering safety, affordability, and non-invasiveness alongside high diagnostic accuracy and substantial concordance with MDCTA.