In patients with exertional limb symptoms and normal ankle-brachial index (ABI) at rest, exercise testing can be used to diagnose lower extremity arterial disease (LEAD). Post-exercise ABI decrease or Exercise transcutaneous oxygen pressure measurement (Exercise-TcPO2) can be used to diagnose LEAD. Objectives were (i) to assess the agreement between both methods (ii) to define the variables associated with the discordance, and (iii) to present results of healthy subjects. In this prospective cross-sectional study, patients with exertional limb symptoms and normal rest ABI were consecutively included. ABI was measured at rest and after standardized exercise protocol as well as Exercise-TcPO2. A kappa coefficient with a 95% confidence interval was used to assess the agreement between the two methods. Logistic regression analysis was performed to outline variables potentially responsible for discordance. Ninety-six patients were included. The agreement between the tests was weak with a k value of 0.23 [0.04–0.41]. Logistic regression analysis found that a medical history of lower extremity arterial stenting (odds ratio 5.85[1.68–20.44]) and age (odds ratio 1.06[1.01–1.11]) were the main cause of discordance. This study suggests that post-exercise ABI and Exercise-TcPO2 cannot be used interchangeably for the diagnosis of LEAD in patients with exertional symptoms and normal rest ABI.