Reservoir compartmentalization is an essential phenomenon in the different life cycles of oilfield production. This concept is crucial for the economic assessment of field development plans because it influences future decisions and designs. Hence, early and fast identification of reservoir compartmentalization is highly appreciated in the oil industry. The routine techniques based on the light-end fraction of crude oil [e.g., gas chromatography (GC) fingerprinting] are relatively time-consuming, high-cost, and sometimes affected by secondary processes. The suggestion of an efficient, straightforward, and rapid technique for obtaining the reservoir architecture, especially in giant and supergiant fields, is an acceptable attempt in the oil industry. Although the concentration of asphaltenes shows a gradient in the reservoir, the chemical composition of these compounds is constant in connected and equilibrated reservoirs. Hence, investigation of the chemical composition of asphaltenes with a precise method for revealing subtle differences comprises the underlying of every efficient method in reservoir continuity assessment. Here, the application of the relative root-mean-square deviation (RMSD) technique on the Fourier transform infrared (FTIR) data was used to compare the structural characteristics of asphaltenes in two case studies (i.e., Ahwaz and Shadegan oil fields) from the Dezful Embayment, southwest Iran. The 12 highest difference characteristic peak ratios were determined in the studied sample suit from the calculated variations in 5 replicates of a sample. The comparison between samples was performed based on these peak ratios, and the RMSD method was used to compare the studied samples. The samples with RMSD values higher than the defined threshold were considered samples with different fingerprints, and these wells will not be communicated during production. Results showed that the Ahwaz and Shadegan fields were subjected to reservoir compartmentalization in the Bangestan reservoir. At least three compartmentalized regions have occurred in the Bangestan reservoir of the Ahwaz field, and two distinct zones are observed in this reservoir from the Shadegan field. The pressure/volume/temperature (PVT) data (i.e., fluid property and composition) and repeat formation tester (RFT) measurements confirmed that these proposed regions in the Ahwaz field are distinct and will not be communicated during production. The FTIR results in the Shadegan field were completely corroborated by PVT and RFT results and indicated two distinct zones with no flow communication during production in the Bangestan reservoir. The obtained results showed that the suggested procedure is robust, trustworthy, simple, rapid, and cost-effective for investigating reservoir compartmentalization.