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Purpose: To compare heart rate (HR), oxygen consumption (VO2), blood lactate (BL), and ratings of perceived exertion (RPE) during arm cycling with and without a blood flow restriction (BFR). Methods: Twelve healthy males (age: 23.9 ± 3.75 years) completed four, randomized, 15-min arm cycling conditions: high-workload (HW: 60% maximal power output), low-workload (LW: 30% maximal power output), low-workload with BFR (LW-BFR), and BFR with no exercise (BFR-only). In the BFR conditions, cuff pressure to the proximal biceps brachii was set to 70% of occlusion pressure. HR, VO2, and RPE were recorded throughout the exercise, and BL was measured before, immediately after, and five minutes post-exercise. Within-subject repeated-measures ANOVA was used to evaluate condition-by-time interactions. Results: HW elicited the greatest responses in HR (91% of peak; 163.3 ± 15.8 bpm), VO2 (71% of peak; 24.0 ± 3.7 ml kg−1 min−1), BL (7.7 ± 2.5 mmol L−1), and RPE (14 ± 1.7) and was significantly different from the other conditions (p < 0.01). The LW and LW-BFR conditions did not differ from each other in HR, VO2, BL, and RPE mean of conditions: ~ 68%, 41%, 3.5 ± 1.6 mmol L−1, 10.4 ± 1.6, respectively; p > 0.05). During the BFR-only condition, HR increased from baseline by ~ 15% (on average) (p < 0.01) without any changes in VO2, BL, and RPE (p > 0.05). Conclusions: HW arm cycling elicited the largest and most persistent physiological responses compared to LW arm cycling with and without a BFR. As such, practitioners who prescribe arm cycling for their clients should be advised to augment the demands of exercise via increases in exercise intensity (i.e., power output), rather than by adding BFR. [ABSTRACT FROM AUTHOR]