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Prior studies have assessed the prognostic value of a decrease, not an increase, of the post-exercise ankle–brachial index (ABI) among patients with normal resting results. Thus, we sought to evaluate the prognostic significance of an increase in post-exercise ABI among these patients. From a single center vascular laboratory database between September 2005 and January 2010, we retrospectively identified 1437 consecutive patients with a normal resting ABI (1.00–1.40) and available post-exercise results. We classified them into group 1 (normal subjects; post-exercise ABI drop ≤ 20%, 58%) and group 2 (post-exercise ABI increase, 42%) after excluding those with an ABI drop > 20% (peripheral artery disease) as they had known disease (n=192). The primary outcome was to assess the risk of ischemic events, defined as a composite of unadjudicated death, stroke, or myocardial infraction (MACE). Associations between groups and outcomes were examined using multivariable Cox proportional hazard and propensity analyses. Both groups had similar prevalence of cardiovascular comorbidities. In unadjusted analysis, group 2 was more likely to have MACE (p = 0.001). After adjusting for all baseline characteristics, an increase in post-exercise ABI compared to normal subjects was associated with a higher MACE (adjusted HR: 1.70, 95% CI: 1.14–2.53; p=0.009). This association stayed statistically significant after propensity matching (adjusted HR: 1.80, 95% CI: 1.17–2.76; p=0.007). This hypothesis-generating analysis showed that an increase in post-exercise ABI appears to identify a population with a higher risk for MACE. A prospective study of this association and mechanisms of risk should be conducted.