The development and management of pressure ulcers (PUs) among hospital and nursing home patients is one of the greatest preventable challenges to healthcare worldwide. For over 50 years, pressure mapping and subjective comfort has been the primary indicators for mattress selection. Our research demonstrates that mattress/patient interface pressure and relative blood/oxygen perfusion do not inversely correlate and pressure is not a meaningful, real-time indicator of tissue ischemia and risk of pressure ulcer development. Developed in our research is a real-time sensor system to simultaneously measure and record these parameters over the anatomical sites at risk for PUs. Measurements focused on the heel, sacrum, trochanter, ischium, scapula and occipital. A modified pressure mapping system is used for interface pressure measurements and integrated with multiple near-infrared sensors to measure specific deep tissue hemoglobin saturated oxygen or rSO2. Testing and mattress design development was done during the period of 2008 to present. Over 200 human tests of commercially available mattresses were conducted in supine, 30 degree, and 70 degree positions, ranging in times of up to four hours. During this time period, we utilized 20 test subjects-eight female and 12 male-with ages ranging from 18 to 65 years. The result of this proprietary off-loading device evaluation and design system shows that the new Oxy-Mat™ (Off-Loading Technologies, Tarrytown, NY) Non-Powered Mattress System consistently provides optimized tissue perfusion as measured by natural deep tissue oxygen saturation levels. In extensive laboratory and clinical evaluations, the Oxy-Mat™ was shown to be functionally superior to CMS Group 2 powered mattresses. Another outcome of our research was that a powered mattress system may not be appropriate for most sensate and semi-ambulatory patients. Further research is underway.