Performance assessments of repositories for the underground disposal of nuclear fuel and waste include models of ground water flow and transport in the host rocks. Estimates of hydraulic conductivity, K, based on field measurements may require adjustment (upscaling) for use in numerical models, but the choice of upscaling approach can be complicated by the use of nested modeling, large-scale fracture zones, and a high degree of heterogeneity. Four approaches to upscaling K are examined using a reference case based on exhaustive site data and an application of nested modeling to evaluate performance assessment of a waste repository. The upscaling approaches are evaluated for their effects on the flow balance between nested modeling domains and on simple measures of repository performance. Of the upscaling approaches examined in this study, the greatest consistency of boundary flows was achieved using the observed scale dependence for the rock domains, measured values from the large-scale interference test for the conductor domain, and a semivariogram regularization based on the Moye model for packer test interpretation. Making the assumption that large fracture zones are two-dimensional media results in the greatest changes to the median of travel time and improves the flow balance between the nested models. The uncertainty of upscaling methods apparently has a small impact on median performance measures, but a significant impact on the variances and earliest arrival times.