We find that OpenEye AM1-BCC and OpenFF NAGL charges result in similar calculated AHFE values, within 1.5 kcal/mol of one another, for 5 out of 6 molecules (Figure ). OpenEye AM1-BCC ELF10 charges which have conformer dependence result in more variable calculated AHFEs with standard deviations of up to 0.7 kcal/mol. OpenFF NAGL charges have no variability and result in less variable calculated AHFEs (i.e. all variation comes from statistical error in the hydration free energy calculations themselves) that seem to converge to a single value with standard deviations of 0.2 kcal/mol. We that OpenFF NAGL partial charges reduce the variation in calculated AHFE G across 5 repeats as compared to AmberTools AM1-BCC charges. This is because OpenFF NAGL charges remove one source of error, variable partial charges. We also find that 2 molecules, lig ejm 31 and lig ejm 43, have variation greater than 1 kcal/mol in calculated AHFE G using NAGL partial charges, suggesting sampling issues contributed to the variation in these molecules (Table ).