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. Earlier lattice physics and reactor 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 carried out 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 filled entirely with advanced fuels could be set up and executed successfully in a CATHENA transient simulation model. The other purpose was to evaluate the peak sheath and peak fuel centerline temperatures during a LOCA to perform an analysis that compares the relative performance of each of the proposed advanced fuels. System T-H simulations with CATHENA were performed to model a postulated LOCA event with a 20% inlet header break in a typical 700-MW(electric)–class PT-HWR using two types of advanced uranium-based and thorium-based fuel bundles in modified 37-element and 35-element geometries. Calculations were also performed for a PT-HWR using conventional natural uranium fuel in 37-element fuel bundles for comparison. In the event of a LOCA, there is a drop in the primary circuit pressure. It is assumed that there is a 2-s delay between the signal of the low primary pressure and the tripping of the reactor. When the reactor trips, the shutdown rods are inserted. The reactor trip is followed by the activation of the emergency core cooling system, which occurs 30 s after the LOCA starts, with a trip signal on the boiler crash cooling. Simulation results for the LOCA demonstrated that the peak fuel centerline temperatures (ranging from 1822°C to 2183°C) were several hundred degrees below the expected melting point of UO2 (~2865°C). Simulations also demonstrated that the peak sheath temperatures for the advanced fuel concepts ranged from 1177°C to 1204°C, which are lower than that with conventional NU fuel in 37-element fuel bundles. Thus, the system T-H analysis of the relative results provides confidence in the proposed advanced uranium-based and thorium-based fuel concepts for potential use in PT-HWRs.