Within the scope of high pressure food sterilization, an important issue that should be taken into account in refining process and equipment design is the time- and position-dependent temperature gradient that exists throughout the pressure vessel and the product load. Since enzymes from thermophilic microorganisms show good prospects for the development of indicators to map out the temperature non-uniformity in high pressure high temperature (HPHT) processing, in this work, the potential of xylanase B from Thermotoga maritima (XTMB) was investigated. Its inactivation at isothermal-isobaric conditions was best described by a first-order model. The pressure dependence of the D values was negligible at HPHT, the temperature dependence however was substantial. The Thermal Death Time (TDT) model, and its corresponding parameters, describing this large temperature dependence were successfully validated under dynamic processing conditions, relevant for industrial HPHT applications.