This study investigated the relationship between blood flow restriction (BFR) cuff pressure and blood flow at rest and during exercise, with the aim of determining if lower cuff pressures will provide an ischemic stimulus comparable to higher pressures. The relationship between blood flow and cuff pressure at rest was determined by measuring blood flow (Doppler Ultrasound) through the superficial femoral artery (SFA) in 23 adults across a range of pressures (0%-100% Arterial Occlusion Pressure at rest [rAOP]). The interplay between cuff pressure, blood flow and exercise was assessed by determining AOP at rest and during plantar flexion exercise (eAOP) and subsequently measuring the blood flow response to plantar flexion exercise with BFR cuff pressure set to either 40% rAOP or 40% eAOP. At rest, a nonlinear relationship between cuff pressure and blood flow through the SFA exhibited a plateau at moderate pressures, with nonsignificant differences in blood flow (~9%, P = 1.0) appearing between pressures ranging from 40% to 80% rAOP. While eAOP was greater than rAOP (229 ± 1.5 mm Hg vs 202 ± 1.5 mm Hg, P < 0.01), blood flow during plantar flexion exercise did not significantly differ (P = 0.49) when applying 40% rAOP or 40% eAOP. Blood flow through the SFA exhibits a nonlinear relationship with cuff pressure, such that cuff pressures in the range of 40% to 80% rAOP reduce blood flow to approximately the same degree. The BFR interventions opting for lower (e.g., 40% AOP), more comfortable pressures will likely provide an ischemic stimulus comparable to that of higher (80% AOP), less-comfortable pressures.