Isometric exercise training (IET) is increasingly cited for its role in reducing resting blood pressure (BP). Despite this, few studies have investigated a potential sham effect attributing to the success of IET, thus dictating the aim of the present study. Thirty physically inactive males (n = 15) and females (n = 15) were randomly assigned into three groups. The IET group completed a wall squat intervention at 95% peak heart rate (HR) using a prescribed knee joint angle. The sham group performed a parallel intervention, but at an intensity (< 75% peak HR) previously identified to be inefficacious over a 4-week training period. No-intervention controls maintained their normal daily activities. Pre- and post-measures were taken for resting and continuous blood pressure and cardiac autonomic modulation. Resting clinic and continuous beat-to-beat systolic (-15.2 +/- 9.2 and -7.3 +/- 5.6 mmHg), diastolic (-4.6 +/- 5 and -4.5 +/- 5.1), and mean (-7 +/- 4.2 and -7.5 +/- 5.3) BP, respectively, all significantly decreased in the IET group compared to sham and no-intervention control. The IET group observed a significant decrease in low-frequency normalized units of heart rate variability concurrent with a significant increase in high-frequency normalized units of heart rate variability compared to both the sham and no-intervention control groups. The findings of the present study reject a nonspecific effect and further support the role of IET as an effective antihypertensive intervention. CLINICAL TRIALS ID: NCT05025202.

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