Background: While the number of people with hypertension (HBP) continues to increase, the therapeutic target for optimal blood pressure (BP) has been revised to a lower level. Studies have suggested that High-Intensity Interval Training (HIIT) could be as efficient as BP-lowering drugs, but no study has compared their efficacy in a randomized trial. The aim of this protocol is to determine if HIIT is as efficient as Hydrochlorothiazide (HCTZ) in lowering 24 h ambulatory BP in prehypertensive older adults. Moreover, the secondary aim is to determine if HIIT is associated with greater cardiovascular and cognitive benefits than HCTZ. Methods: This study is an interventional, single-center, non-inferiority trial, with two randomized parallel groups of prehypertensive participants aged 60 years or more. One group will be prescribed daily doses of 12.5 mg of HCTZ for 12 weeks, and the other group will follow thrice-weekly HIIT for 12 weeks. Each group will be composed of 30 participants. The primary outcome is 24 h ambulatory BP. Secondary outcomes are scores on neuropsychological assessments, balance and gait performances, maximal oxygen uptake, peripheral endothelial function, and arterial stiffness. Non-inferiority tests will be performed on the primary outcome, and secondary outcomes will be compared using independent t-tests. Conclusion: This study will determine if HIIT is at least as efficient as HCTZ in lowering BP in prehypertensive older adults. This study will also determine if HIIT provides greater benefits in terms of cardiovascular and cognitive status (NCT04103411).