Abstract:  The potential use of Thermomyces lanuginosus xylanase to develop a pressure–temperature–time integrator (PTTI) for high pressure processing was investigated. The combined effect of pressure and temperature on the inactivation of xylanase was studied in the pressure range of 100 to 600 MPa and temperature range of 50 to 70 °C. A synergistic effect of pressure and temperature was observed. Xylanase inactivation at the studied processing conditions followed first‐order kinetics and was found to be very sensitive to changes in pressure and temperature. The values of activation energy and activation volume were estimated as 92.8 kJ/mol and −23.3 mL/mol at a reference pressure of 450 MPa and a reference temperature of 60 °C, respectively. A mathematical model of xylanase inactivation, having as variables time, pressure, and temperature allows the calculation of remaining enzyme activity at any combination of processing conditions within the studied domain. Practical Application:  To ensure the optimization and control of high pressure processing, evaluation of the process impact on both safety and quality attributes of foods is essential. Enzymes can serve as effective tools in evaluating the impact of high pressure processes of foods.