Tourniquet use creates a reduced blood surgical field during total knee arthroplasty (TKA), however, prolonged ischemia may cause postoperative tourniquet complications. To understand the effects of tourniquet-induced ischemia, we performed a prospective observational study using quantitative broadband diffuse optical spectroscopy (DOS) to measure tissue hemodynamics and water and lipid concentrations before, during, and after tourniquet placement in subjects undergoing TKA. Data was collected for 6 months and, of the total subjects analyzed (n = 24), 22 were primary TKAs and 2 were revision TKA cases. We specifically investigated tourniquet-induced hemodynamics based upon subject-specific tissue composition and observed a significant relationship between the linear rate of deoxygenation after tourniquet inflation and water/lipid ratio (W/L, p < 0.0001) and baseline somatic tissue oxygen saturation, StO₂ (p = 0.05). Subjects with a low W/L ratio exhibited a lower tissue metabolic rate of oxygen consumption, (tMRO₂) (p = 0.008). Changes in deoxyhemoglobin [HbR] (p = 0.009) and lipid fraction (p = 0.001) were significantly different between high and low W/L subject groups during deoxygenation. No significant differences were observed for hemodynamics during reperfusion and total tourniquet time was neither significantly related to the hemodynamic hyperemic response (p = 0.73) nor the time to max StO₂ after tourniquet release (p = 0.57). In conclusion, we demonstrate that DOS is capable of real-time monitoring of tissue hemodynamics distal to the tourniquet during TKA, and that tissue composition should be considered. DOS may help surgeons stratify hemodynamics based upon tissue composition and eventually aid the preoperative risk assessment of vascular occlusions from tourniquet use during TKA.