OBJECTIVE To examine the effects of low-load knee extensor training to fatigue with and without blood flow restriction (BFR) on calf vascular conductance, calf venous compliance, and peripheral arterial stiffness in middle-aged individuals. METHODS Eleven men (55 ± 8 years) and five post-menopausal women (57 ± 5 years) completed 6 weeks of unilateral knee extensor training with one limb exercising with BFR (BFR limb) and the contralateral limb exercising without BFR (free flow, FF limb). Before and after the training, femoral pulse wave velocity (PWV), calf blood flow (normalized as conductance), and calf venous compliance were measured in each limb. RESULTS PWV increased following training in both limbs (main effect of time, p = 0.036; BFR limb 8.9 ± 0.8 vs. 9.5 ± 0.9 m/s, FF limb 9.0 ± 1.2 vs. 9.0 ± 1.1; Pre vs. Post). Calf blood flow increased (p = 0.026) in the FF limb (25.0 ± 7.0 vs. 31.8 ± 12.0 flow/mmHg; Pre vs. Post) but did not change (p = 0.831) in the BFR limb (29.1 ± 11.3 vs. 28.7 ± 11.5 flow/mmHg; Pre vs. Post). Calf venous compliance did not change in either limb following training. CONCLUSIONS These results suggest low-load BFR resistance training to fatigue elicits small increases in peripheral arterial stiffness without eliciting concomitant changes in venous compliance. In addition, unlike low-load knee extensor training without BFR, training with BFR did not enhance calf blood flow.