Newly designed double-compartment tourniquet cuff with asymmetric pressure distribution (DCAP) and standard single-compartment tourniquet cuff with symmetric pressure distribution (SCSP) were tested on 17 healthy volunteers (27.3±5.2 years) during rest. Thigh circumference and skinfold were determined for each leg. Efficiency of tourniquets was compared bilaterally on proximal thighs at four occlusion pressures (OP = 120, 160, 200 and 240 mmHg). Changes in hemoglobin kinetics in v. lateralis muscle (near-infrared spectroscopy), cardiovascular responses (ECG and ABP), isometric endurance, maximal voluntary isometric contraction (MIVC) torque and pain intensity (visual analogue scale, VAS) were analyzed. Lean thigh circumference did not differ between legs (L= 57.3±3.7 cm, R=57.1±3.8 cm). VAS scores did not differ between tested tourniquets, but did significantly increase (p=0.03) at OP 200 mmHg and higher. Difference (p = 0.009) in slope of total hemoglobin concentration change ([tHbs]) was found between the tourniquets at OP 160 mmHg (DCAP=0.028μM/s, SCSP=0.056μM/s). Mean ABP was significantly increased (p= 0.02) at OP 120 mmHg compared to baseline values, whereas change in heart rate was detected. MIVC did not differ between legs (L= 230 ± 77 Nm, R= 233 ± 77 Nm). Shorter time to exhaustion (-11%; p=0,003) was found in ischemic condition compared to control condition, while no difference was found between tested tourniquets. Based on differences in [tHbs], arterial occlusion was induced at OP ≥ 160 mmHg with DCAP, whereas OP ≥ 200 mmHg was required with SCSP. Given that higher pressure may cause damage to underlying tissues and increases discomfort, it is concluded that novel tourniquet design allows safer and more efficient blood flow restriction at a given tourniquet pressure and discomfort during rest. Whether the same is achieved during BFRRE, needs further investigation.