Background Negative-pressure wound therapy (NPWT) is believed to accelerate wound healing by altering wound microvascular blood flow. Although many studies using laser Doppler have found that NPWT increases perfusion, recent work using other modalities has demonstrated that perfusion is reduced. The purpose of this study was to investigate the influence of NPWT on tissue oxygenation of the foot, which is the most sensitive region of the body to ischemia. Methods Transcutaneous partial pressure of oxygen (TcpO₂) was used to determine perfusion beneath NPWT dressings of 10 healthy feet. The sensor was placed on the tarso-metatarsal area of the foot and the NPWT dressing was placed above the sensor. TcpO₂ was measured until it reached a steady plateau state. The readings obtained at the suction-on period were compared with the initial baseline (pre-suction) readings. Results TcpO₂ decreased significantly immediately after applying NPWT, but gradually increased over time until reaching a steady plateau state. The decrease in TcpO₂ from baseline to the steady state was 2.9 to 13.9 mm Hg (mean, 9.3±3.6 mm Hg; 13.5±5.8%; P<0.01). All feet reached a plateau within 20 to 65 minutes after suction was applied. Conclusions NPWT significantly decrease tissue oxygenation of the foot by 2.9 to 13.9 mm Hg. NPWT should be used with caution on feet that do not have adequate tissue oxygenation for wound healing.