In principle, free energy differences associated with different pathways should be averaged with some weights, and those weights should depend on the overlap between the conformational ensembles sampled in the US simulation along the particular pathway. While such reweighing might be possible, it will require the development of a new formalism and software. The simple reweighing techniques discussed here, led to differences in the estimated free energies of 4.7 kcal/mol, which is below the 12 kcal/mol maximal difference between repeats. However, the differences between the various reweighing techniques are higher than the error for the individual reweighting (≈ 1.5 kcal/mol). Without a physical argument in favor of a specific reweighting approach, it remains unclear how to extract meaningful free energy estimates from multiple US repeats.