Centrifugal compressors are the most prevalent units in any gas processing plant. Optimizing the efficiency and maximizing the reliability of these machines are of utmost importance for sustaining feasible plant production. This thesis research introduces a step-by-step approach to assessing the aerothermodynamic performance of process centrifugal compressors. Leveraging recent advances in real gas theoretical principles, the approach relies on the GERG-2008 equation of state for calculating the gas thermodynamic properties, accommodating complex compositions of up to 21 components. Furthermore, the considered methodology uses the Huntington FourPoint method for evaluating the polytropic head and efficiency of the compressor section. The accuracy and convergence of the developed algorithm were investigated after it was developed into a computer program. The developed approach was also compared with literature records using three comparative approaches: relative error, linear regression, and paired t-test. The outcomes of these comparisons revealed unwavering conformity between the obtained results and their counterparts in the literature. The maximum deviation in thermodynamic properties was 0.5% for isobaric heat capacity. For polytropic efficiency, the maximum deviation was 0.016%. Moreover, the proposed methodology was applied on two industrial cases, in which the developed algorithm was used to diagnose oil ingress and deposit accumulation in natural gas centrifugal compressors. The proposed methodology proved its robustness in identifying machine underperformance that otherwise could not be identified as accurately using the existing practices and maintenance protocols by the local compressor end-users. The developed algorithm provides a robust solution for the endusers for carrying out instantaneous and highly accurate performance assessments.