Despite very similar protein structures, ascorbate peroxidase (APX) and yeast cytochrome c peroxidase (CCP) stabilize different radical species during enzyme turnover. Both enzymes contain similar active site residues, including the tryptophan that is oxidized to a stable cation radical in CCP. However, the analogous tryptophan is not oxidized in APX, and the second oxidizing equivalent is retained as a porphyrin pi-cation radical. This difference between CCP and APX is thought to contribute to the different substrate specificities of the two proteins. Electrostatic destabilization by a nearby cation has been proposed to be partially responsible for this difference. In this study we provide an improved computational approach to estimate the contribution of solvent and protein electrostatics to the energetics of tryptophan cation radical formation in the two enzyme environments. The protein dipoles Langevin dipoles (PDLD) model is combined with molecular dynamics to estimate the role of discrete solvation, atomic polarizabilities, and dynamic motional averaging on the electrostatic potentials. Partial charges for the tryptophan cation radical used Merz-Kollman ESP charges fit to the electrostatic potential of 3-methylindole cation radical, which in turn was calculated using density functional methods, a Becke3LYP functional, and the 6-31G* basis set. The PDLD model shows that the protein environment of CCP stabilizes the tryptophan cation radical by 330 mV relative to that in APX. Analysis of the components contributing to this difference supports proposals that the cation binding site contributes to, but is not the sole cause of, the different sites of radical stabilization. The enzymes have thus evolved this distinction using several contributing interactions including the cation binding site, solvent access, and subtle differences in protein structure and dynamics.