BACKGROUND: Current guidelines recommend aggressive management of hypertension. Recent evidence suggested potential harm with low blood pressure targets in patients with peripheral artery disease. We investigated the association of a history of hypertension and office systolic blood pressure (SBP) with major adverse cardiovascular events (MACEs) and major adverse limb events (MALEs). METHODS AND RESULTS: The EUCLID trial (Examining the Use of Ticagrelor in Peripheral Artery Disease) included 13 885 participants with symptomatic peripheral artery disease; median follow-up was 30 months. Cox proportional hazards regression was used to calculate hazard ratios (HRs) for any MACE, MALE, and MALE including lower extremity revascularization. A clinical history of arterial hypertension was present in 10 857 (78%) participants, and these participants were older and more likely to be female when compared with the 3026 (22%) patients without hypertension. In patients with a history of hypertension, the adjusted hazard ratio for MACE was 0.94, 95% CI, 0.82-1.08; P=0.39, and the adjusted hazard ratio for MALE was 1.08, 95% CI, 0.96-1.23; P=0.21. During follow-up, average SBP was 135 mm Hg (125-145). Every 10 mmHg increase in SBP>125 mmHg was associated with an increased risk of MACE (HR, 1.10 [95% CI, 1.06-1.14]; P<0.001), a marginally increased risk of MALE (HR, 1.07 [95% CI, 1.00-1.15]; P=0.062), and an increased risk of MALE/lower extremity revascularization (HR, 1.08 [95% CI, 1.04-1.11]; P<0.001). Every decrease in 10 mmHg SBP ≤125 mmHg was associated with an increased risk of MACE (HR, 1.19 [95% CI, 1.09-1.31]; P<0.001) but not MALE or MALE/lower extremity revascularization (HR, 1.02 [95% CI, 0.84-1.23], P=0.824; HR, 1.04 [95% CI, 0.95-1.13], P=0.392, respectively). CONCLUSIONS: History of hypertension was not associated with higher hazard for MACE or MALE in patients with peripheral artery disease. In contrast, there was a higher hazard of MACE in patients with out-of-target low and high SBP. High but not low SBP was associated with an increased risk of ischemic limb events. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01732822.