High pressure thermal (HPT) processing is a candidate technology for achieving commercial sterility of low acid shelf-stable and chilled food products. A major food safety challenge to the implementation of HPT lies in achieving temperature uniformity inside the vessel during processing. Computational Fluid Dynamics (CFD) modelling can be used to predict locally specified temperature profiles arising during HPT processing, but it is essential that such models are validated, and that predictions agree well with temperatures measured in actual processes. In this work, the effects of variations in inputs for compression fluid properties and process conditions (i.e., the applied pressure profiles) on the prediction accuracy of a CFD model for a Stansted 3.6 L Isolab HPTS system were studied. Good agreement was found between simulated and measured temperature distributions when accurate compression heating coefficients for the compressed materials and actual pressure profiles were used as inputs of the model. Inaccurate approximations of these values and conditions resulted in much less useful models, highlighting the importance of attention to detail in input data for CFD models of HPT processing, in these still early stages of development of the technology. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.