Various computational models of trifluoroethanol (TFE) and water have been explored with the goal of finding a system for molecular dynamics (MD) simulations that reliably predict properties of 40% TFE water (v/v) and can be used in studies of peptide solvent nuclear cross-relaxation. Models derived by modification of TFE parameters developed by Fioroni et al. (J. Phys. Chem. B 2000, 104, 12347), in combination with either TIP4P-Ew or TIPSP-E water, were most successful. Simulations of 40% TFE TIP4P-Ew water evidenced separation of the system into large TFE-rich and water-rich domains. With TIPSP-E water, simulations showed aggregation of each solvent component into small clusters. Nuclear spin dipolar interactions between solvent fluorines and the methyl hydrogens of acetate ion dissolved in 40% TFE water were calculated. The cross-relaxation parameter sigma(HF) reckoned for the TFE TIPSP-E system agreed with experiment while the value calculated using the TFE-TIP4P-Ew system was too low. While the TFE-TIP5P-E model of 40% TFE water leads to good predictions of the system density, translational diffusion coefficients, and a solvent solute cross-relaxation parameter, this model performs poorly in predicting the enthalpy of mixing. Preliminary studies of 20% TFE water and 50% TFE-water suggest that the model will perform with the same characteristics for mixtures that have compositions near 4096 TFE-water.