This paper investigates the effects of various primary reference fuel (PRF) blends, compression ratios, and intake temperatures on the thermodynamics and performance of homogeneous charge compression ignition (HCCI) combustion in a CFR engine. Combustion phasing was kept constant at a CA50 phasing of 5° aTDC and the equivalence ratio was kept constant at 0.3. Meanwhile, the compression ratio varied from 8:1 to 15:1 as the PRF blends ranged from pure n-heptane to nearly pure isooctane. The intake temperature was used to match CA50 phasing. In addition to the experimental results, a GT-Power model was constructed to simulate the experimental engine and the model was validated against the experimental data. The GT-Power model and simulation results were used to help analyze the energy flows and thermodynamic conditions tested in the experiment.The results indicate that an increase of compression ratio causes higher thermal efficiency and fuel conversion efficiency; however, at the same compression ratio, an increase in PRF number results in lower efficiency due to the required increase in intake temperature and the associated decrease in charge density. While the efficiency does increase with compression ratio, the results show that the effect of increased expansion work is partially offset by higher heat transfer losses and lower ratios of specific heats at higher compression ratios. The results indicate that the maximum pressure rise rate (MPRR) in HCCI significantly increases with compression ratio. Combustion efficiency shows a strong trend with peak temperature regardless of the PRF number or compression ratio, indicating that the CO to CO2 conversion is independent of the parent fuel chemistry in the case of the primary reference fuels; whereas the unburned hydrocarbon emissions showed the opposite trend, depending mostly on the parent fuel’s autoignition tendency.