In this paper, some thermophysical properties of light and heavy water will be predicted and modeled using virial equation of state (VEOS) and, effect of isotopic substitution will be studied. In this respect, by fitting the experimental and theoretical data of the second virial coefficient of light and heavy water in the temperature range of 300 to 1800 K, a new equation will be presented, using which the thermodynamic properties of the aforementioned fluids will be predicted. The obtained results are compared with experimental data to evaluate the model and the new equation of second virial coefficient. The results show that this approach has a very good ability to predict thermophysical properties of light and heavy water. It will also be shown that deuterium isotopic substitution reduces the attractive interaction between molecules, especially above the critical temperature, and this causes the difference in the thermodynamic properties of the two fluids. Calculations performed in the above temperatures and pressures range using virial coefficients in order to determine thermophysical properties of light and heavy water and also investigation of the effect of isotopic substitution are novelties of this article.