Remote ischemic preconditioning (RIPC) can attenuate tissue damage sustained by ischemia-reperfusion injury. Blood flow restriction exercise (BFRE) restricts blood flow to exercising muscles. We implemented a novel approach to BFRE with cyclical bouts of blood flow restriction-reperfusion, reflecting the RIPC model. A concern about BFRE, however, is potential amplification of the exercise pressor reflex, which could be unsafe in at-risk populations. We hypothesized that cyclical BFRE would elicit greater increases in sympathetic outflow and arterial pressure than conventional exercise (CE), performed at the same relative intensity. We also assessed the cerebrovascular responses, due to potential implementation of BFRE in stroke rehabilitation. Fourteen subjects performed treadmill exercise at 65-70% HR_max with and without intermittent BFR (4x5-min intervals of bilateral thigh-cuff pressure followed by 5-min reperfusion periods). Mean arterial pressure (MAP), plasma norepinephrine (NE), and middle and posterior cerebral artery velocities (MCAv and PCAv) were compared between trials. As expected, BFRE elicited higher [NE] compared to CE (1249±170 vs 962±114 pg/ml; P=0.06). Unexpectedly, however, there were no differences in MAP between conditions (overall P=0.33), and MAP was 4-5 mmHg lower with BFRE vs. CE during the reperfusion periods (P≤0.05 for reperfusion periods 3 and 4). There were no differences in MCAv or PCAv between trials (P≥0.22), suggesting equivalent cerebro-metabolic demand. The exaggerated sympatho-excitatory response with BFRE was not accompanied by higher MAP, likely due to the cyclical reperfusions. This cyclical BFRE paradigm could be adapted to cardiac- or stroke-rehabilitation, where exercising patients could benefit from the cardio- and cerebro-protection associated with RIPC.