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Background: Early diagnosis of acute compartment syndrome (ACS) of the leg is essential to improve the outcome. Direct invasive measurement is currently recommended to measure intracompartmental pressure. A non-invasive and reproducible means of making the diagnosis would be a step forward. The purpose of this exploratory study was to investigate the feasibility of non-invasive ultrasound-guided angle measurement as a surrogate of increased pressure in a model of ACS. Methods: A model of ACS was generated by infusion of saline into the anterior compartment of the leg of human cadavers to incrementally increase the intracompartmental pressure from 10 to 100 mmHg. In 40 legs (20 cadavers), the angle (TFA, tibia-fascia angle) between the anterolateral cortex of the tibia and the fascia of the anterior compartment was measured at each 10 mmHg pressure increase using ultrasound in a standardized transversal plane. A multilevel linear regression model was used to estimate intracompartmental pressure from delta TFA (ΔTFA). Results: TFA (mean [± SD]) increased from 61.0° (± 12.0°) at 10 mmHg up to 81.1° (± 11.1°) at 100 mmHg compartment pressure. Each increase ΔTFA by one degree was associated with an increase in pressure by 3.9 mmHg (95% CI, 3.8–4.0, p < 0.001). Conclusions: We found that intracompartmental pressure of the anterior compartment of the calf can be well estimated by ultrasound-based ΔTFA in this post mortem experiment. Our findings indicate that non-invasive TFA measurement is feasible and it is reasonable that this will hold true in real life, but the findings are too preliminary to be used in clinical practice now. [ABSTRACT FROM AUTHOR]