In this paper, a generalized methodology has been developed to determine the diffusion coefficient of supercritical CO 2 in cores that are saturated with different oil samples, under reservoir conditions. In theory, a mathematical model that combines Fick's diffusion equation and the Peng-Robinson equation of state has been established to describe the mass transfer process. In experiments, the pressure decay method has been employed, and the CO 2 diffusion coefficient can be determined once the experimental data match the computational result of the theoretical model. Six oil samples with different compositions (oil samples A to F) are introduced in this study, and the results show that the supercritical CO 2 diffusion coefficient decreases gradually from oil samples A to F. The changing properties of oil can account for the decrease in the CO 2 diffusion coefficient in two aspects. First, the increasing viscosity of oil slows down the speed of the mass transfer process. Second, the increase in the proportion of heavy components in oil enlarges the mass transfer resistance. According to the results of this work, a lower viscosity and lighter components of oil can facilitate the mass transfer process.Energies 2018, 11, 1495 2 of 20 methods for the quantitative determination of the gas (N 2 , CO 2 , CH 4 [28], C 2 H 6 , C 3 H 8 , or a mixture gas) diffusion coefficient in crude oil. These methods include the pressure decay method, X-ray computer-assisted tomography (CAT) method, magnetic resonance imaging (MRI) method [29,30], dynamic drop volume analysis (DPDVA), and pore-scale network modeling method. All of these methods have advantages and flaws:Direct testing method. Hill and Lacey [31] tested the diffusion coefficient of CH 4 in isopentane with a constant pressure method in a Pressure-Volume-Temperature (PVT) system. Sigmund [32] also used this method to study the binary dense gas diffusion coefficients under reservoir conditions. Islas-Juarez et al. [33] set up an experimental device to determine the effective diffusion coefficient of N 2 in a sandpack model. They devised a special setting to sample crude oil that was dissolved with N 2 in their porous model. The samples were then analyzed by gas chromatograph, and the gas concentration in the oil phase was determined. The corresponding diffusion coefficient was determined by matching the mathematical diffusion model with the experimentally measured concentration curve. The main shortcomings of the direct testing method for the solvent diffusion coefficient are that it is both time and labor consuming, which results in an expensive process.Pressure decay method. Riazi [34] proposed a technique known as the pressure decay method based on the fact that the pressure of the gas phase in a closed diffusion cell decreases with the migration of the gas phase into the liquid phase. One of the remarkable features of this method is that it does not require costly component measurements. In the following two decades, many scholars adopted this method to test the diffus...