Strength training responses are influenced by sets, repetitions, and mechanical load, whereas Blood Flow Restriction (BFR) training adds the variable of temporarily restricting blood flow via a tourniquet. This has intensified scientific discussions regarding the vascular responses and thereby safety of the BFR method. To address these concerns, we investigated intravascular pressure changes during low-load (LL-RT), low-load with BFR (LL-BFR-RT), and high-load (HL-RT) exercise. Ten healthy men (26.8 ± 4.59 years) performed unilateral biceps curls to failure in a randomized cross-over design: (1) LL-RT (30% 1RM), (2) LL-BFR-RT (30% 1RM, 50% LOP), and (3) HL-RT (75% 1RM). Total workload was significantly higher in LL-RT (692 ± 251 kg) compared to LL-BFR-RT (378 ± 58.7 kg) and HL-RT (327 ± 65.1 kg, p <
0.001). In terms of mean values, LL-BFR-RT resulted in higher diastolic and mean arterial pressures during rest periods between sets compared to other conditions (p ≤ 0.02). Both LL-RT and LL-BFR-RT led to longer durations spent at increased diastolic (above 90 mmHg, LL-RT: ~419 s vs. LL-BFR-RT: ~356 s vs. Hl-RT: ~122 s), systolic (above 140 mmHg, LL-RT: ~437 s vs. LL-BFR-RT: ~336 s vs. HL-RT: ~199 s), and mean arterial pressures (above 107 mmHg, LL-RT: ~451 s vs. LL-BFR-RT: ~384 s vs. HL-RT: ~168 s) compared to HL-RT (p ≤ 0.028). Relative to total exercise time, LL-BFR-RT resulted in higher proportion of time spent at elevated diastolic (above 90 mmHg, LL-RT: ~56.5% vs. LL-BFR-RT: ~68.7% vs. Hl-RT: ~33.5%) and mean arterial pressures (above 107 mmHg, LL-RT: ~60.8% vs. LL-BFR-RT: ~74.0% vs. HL-RT: ~45.7%) compared to HL-RT (p ≤ 0.034). Peripheral venous pressure was significantly higher in LL-BFR-RT compared to other conditions (p <
0.001), with both absolute and relative time spent at higher pressures (above 75 mmHg, LL-RT: ~57.0 s and ~ 9.12% vs. LL-BFR-RT: ~424 s and ~ 81.7% vs. HL-RT: ~36.0 s and ~ 8.99%, p ≤ 0.002). Our results suggest that BFR training performed to failure imposes greater arterial and venous stress in the exercising limb compared to high-load training without BFR, particularly due to prolonged exposure to elevated pressures. Further research is needed to assess the potential risks of elevated local arterial and venous pressure responses by frequent BFR use, particularly in populations with pre-existing medical conditions.