While an equation of state (EOS) plays a critical role in estimating thermodynamic properties, employing it in the determination of binary interaction parameters is extremely important. In general, these parameters can be determined from phase equilibrium data. However, data collection from experiments is a time-consuming and tedious process. In this study, after measuring the excess enthalpies of binary systems containing CO2 by high-pressure flow isothermal microcalorimetry (IMC), we determined the EOS binary interaction parameters, specifically, the Peng-Robinson EOS binary interaction parameters. These binary interaction parameters obtained by IMC were compared with those obtained by vapor-liquid equilibrium (VLE) experiments. Hence, high-pressure flow IMC appears to be an effective method for the determination of interaction parameters that are used in the estimation of thermodynamic properties. Further, the Flory-Huggins interaction parameters of a binary mixture CO2 containing with various mole compositions were also estimated by employing high-pressure IMC.