Background: Free tissue transfer necessitates vigilant postoperative monitoring for vessel occlusion. Unfortunately, most monitoring methods require experienced personnel and are expensive to use. Furthermore, many tests have low sensitivity, low specificity, or significant delay between vessel occlusion and detection. The authors report on a novel method of tissue monitoring that avoids these limitations by tracking interstitial glucose concentration. Methods: Vertical rectus abdominis myocutaneous flaps were elevated in adult rats based on the superior epigastric vessels. Interstitial glucose within the flaps was monitored using a transcutaneous sensor. Interstitial glucose was recorded following arterial occlusion in 10 flaps and venous occlusion was recorded in eight flaps. Criteria for detecting vessel occlusion were developed based on interstitial glucose concentration and rate of change. Results: Occlusion of the flap/s arterial supply led to a rapid decline in interstitial glucose. Within 15 minutes of arterial occlusion, the interstitial glucose in occluded flaps was significantly lower than in viable flaps (p = 0.0003). Occlusion of venous outflow resulted in a similar decline of interstitial glucose. Interstitial glucose below the animal/s euglycemic range was 100 percent sensitive (95 percent confidence interval, 78.1 to 100 percent) and 95.2 percent specific (95 percent confidence interval, 74.1 to 99.8 percent) for vessel occlusion. A fall in interstitial glucose greater than or equal to 7 mg/dl per minute was 100 percent sensitive (95 percent confidence interval, 78.1 to 100 percent) and 100 percent specific (95 percent confidence interval, 80.8 to 100 percent) for vessel occlusion. The delay between occlusion and detection was less than 30 minutes for all flaps. Conclusions: Interstitial glucose monitoring is highly sensitive and specific for vessel occlusion. This technology offers a rapid, inexpensive, and accurate method of monitoring free tissue transfers. Copyright © 2010 by the American Society of Plastic Surgeons.