[en] This work examines the possible migration of radionuclides from a deep geologic nuclear waste repository sited in fractured crystalline host rock. The key safety concern is the potential effect on waste isolation of the inter-connectivity of the fracture network, which is primarily established by the temporal evolution of the temperature and stress fields at the time of original rock intrusion and cooling. Two end members are considered in these simulations, one with a high degree of connectivity to the biosphere, such that advective transport through the fracture and fault network controls radionuclide migration, and the other with a low degree of connectivity, such that slow diffusive transport through the crystalline rock matrix is the controlling process for radionuclide migration to the biosphere. Both end members have several areally extensive, high-transmissivity deformation zones, whose distance to the repository is an important factor for waste isolation capability. Uncertainties in fracture properties (transmissivity, orientation, radius) and fracture distribution also give rise to uncertainty in waste isolation capability (i.e., the overall connectivity of the repository with the surface biosphere). These types of natural system uncertainties are generally present in any geologic site-characterization program and thus represent an important factor in assessing repository performance in hard rock environments. The waste considered in these simulations are spent fuel rod assemblies from the U.S. commercial nuclear reactor fleet. Thermal output of the waste must be considered in the simulations and can influence the rate and timing of waste package failure, waste form degradation, and fluid flux due to thermal expansion around the repository horizon. To achieve a high-fidelity representation of radionuclide transport in fractures and rock matrix, combined with thermal energy transport and fluid flow in fractures and matrix, the mathematical model is solved numerically in a parallel high-performance computing (HPC) environment on a finite volume unstructured grid consisting of approximately 5 million cells, using Geologic Disposal Safety Assessment (GDSA) Framework (https://pa.sandia.gov), an open-source performance assessment tool for deep underground disposal of nuclear waste. GDSA Framework uses PFLOTRAN to solve the balance equations on a three-dimensional grid with heterogeneous properties, using multiple processors in a parallel configuration based on domain decomposition. The fracture networks in these simulations are originally generated as discrete fracture networks (DFNs), which are sets of two-dimensional planes distributed in a three-dimensional domain. The method used in GDSA Framework maps the stochastically generated DFN to an equivalent continuous porous medium (ECPM) domain that allows for the simulation of coupled heat flow, fluid flow, and radionuclide transport, including heat conduction through the matrix of the fractured rock, which is a process not easily modeled in a DFN representation. Computational efficiency is also greatly enhanced using the ECPM method, allowing for a realistic representation and analysis of uncertainties in a multi-realization performance assessment of a deep geologic repository. The effect of fracture connectivity on the waste isolation safety function, as brought to light by these GDSA Framework simulations, points to the importance of including a realistic representation of uncertainties in fracture properties and distribution (effectively, uncertainty in spatial heterogeneity) in repository safety assessment simulations. (authors)