This work represents the first clinical data acquired with the endoscopic laser speckle imaging (eLSPI) system, a new diagnostic tool developed for real-time imaging of tissue blood flow during endoscopic surgical procedures. eLSPI was used to image tissue perfusion in the medial compartment of the knee of five patients requiring arthroscopic knee surgery. The effectiveness of eLSPI as a diagnostic tool was tested by measuring changes in tissue perfusion resultant from tourniquet application, and intra-articular epinephrine. eLSPI produced real-time perfusion video images of tissue blood flow in the knee joint. Tourniquet applications produced consistent decreases in mean perfusion index measurements (29.3%±5.1% in meniscus; 39.5%±8.2% in synovium with an intra patient variability of 6%-9%). A dose-dependent vasoconstrictive response to the administration of intra-articular epinephrine was measured, with maximum dose producing a mean decrease in perfusion of 31.0%-9.3% in meniscus and 41.2%-10.9% in synovium. eLSPI consistently detects decreases in articular tissue blood flow resultant from tourniquet inflation or from the administration of increasing concentrations of epinephrine. These are the first in vivo results indicating physiologic changes in articular tissue as a function of two commonly applied practices in endoscopic joint surgery.