This study investigated the effects of frequent low-load ischemic resistance exercise performed to failure on quadriceps size and performance, muscle activation, oxygen kinetics and cardiovascular responses. Ten healthy males performed knee-extension exercise for 4 weeks (4 sessions/week) at 15% maximal voluntary muscle contraction (MVC). One leg was trained with free blood flow (C-leg) while in the other leg (I-leg) ischemia was induced by an inflatable cuff (≥230 mmHg). Quadriceps cross-sectional area (CSA) of the I-leg increased by 3.4% (P<0.05). A tendency for smaller increase in muscle CSAs at the cuff level was observed. MVC force did not change in either leg, whereas the number of repetitions during exercise test to failure increased (P<0.01) by 63% in I-leg and 36% in C-leg. The decrease in muscle oxygenated hemoglobin concentration acquired by NIRS was attenuated (P<0.01) by 56% in I-leg and 21% in C-leg. Electromyographic amplitude of rectus femoris in I-leg was ∼45% lower (P<0.025) during the ischemic test. Also, ∼9% increase (P<0.05) in pre-exercise diastolic pressure was observed. In conclusion, substantial gains in muscle endurance capacity were induced, which were associated with enhanced muscle oxygen delivery. The potential negative effects of ischemic exercise with high cuff pressure on muscle and nerve and on arterial pressure regulation need further investigation.