- There is evidence that carpal tunnel syndrome (CTS) development is driven by vascular factors, specifically those resulting from ischemia and edema. The purpose of this study was to investigate the vascular hypothesis of CTS development by quantifying the temporal effects of 30 min of sub-diastolic brachial blood flow occlusion on median nerve edema, intraneural blood flow velocity, nerve function as measured through nerve conduction study (NCS), tendon-connective tissue mechanics and carpal tunnel tissue stiffness. Forty healthy volunteers underwent 30 min of sub-diastolic brachial occlusion while an NCS and ultrasound examination were performed consecutively every 5 min. Motor latency (p < 0.001), sensory conduction velocity (p < 0.001), sensory amplitude (p = 0.04), nerve blood flow (p < 0.001), peak relative flexor digitorum superficialis tendon-sub-synovial connective tissue displacement (p = 0.02) and shear strain (p = 0.04) were significantly affected by partial ischemia. Our results highlight the dependency of carpal tunnel tissue function on adequate blood flow.