The use of advanced uranium-based and thorium-based fuel bundles in pressure tube heavy water reactors (PT-HWRs) has the potential to improve the utilization of uranium resources while also providing improvements in performance and safety characteristics of PT-HWRs. Previous lattice physics and core physics studies have demonstrated the feasibility of using such advanced fuels; however, thermal-hydraulic (T-H) studies are required to confirm that these advanced fuels will have adequate T-H safety margins. Preliminary system T-H transient simulations have been performed for a 700-MW(electric)–class PT-HWR in a postulated loss-of-coolant accident (LOCA) using the CATHENA code. One purpose of this work was to demonstrate that such simulations of a PT-HWR with advanced fuels could be set up and executed successfully in a CATHENA transient simulation model. The other purpose was to evaluate the peak fuel sheath and fuel centerline temperatures in two designated fuel channels containing advanced uranium-based or thorium-based fuel during a LOCA transient event. In the CATHENA simulation models, a PT-HWR core is fueled with conventional 37-element natural uranium fuel bundles in 378 out of 380 fuel channels while two designated fuel channels, the channel with the highest total power and the channel containing the bundle with the highest power level, are filled with various types of advanced fuels. Results indicate that setting up these models is feasible and that the predicted peak fuel centerline temperatures and peak sheath temperatures for the advanced fuel channels are well below the fuel melting points and the rapid oxidation temperature for the Zircaloy-4 sheath/clad (~1200°C), respectively. These preliminary results provide confidence that the advanced fuels will likely have adequate T-H safety margins in a transient LOCA event in a PT-HWR. These results set the stage for more detailed and comprehensive system T-H models of PT-HWRs fueled entirely with advanced uranium-based or thorium-based fuels.