2,2,4-Trimethylpentane, also known as isooctane, is used as one of the model fuel species on spark and homogeneous charge compression ignition engines. This study presents thermochemical and kinetic properties in the oxidation of the secondary isooctane radical, which includes the peroxy radical formed from the 3O2 association, the hydroperoxy alkyl radicals formed from the intramolecular hydrogen transfers, and the products formed from reactions of the hydroperoxy alkyl radicals. Geometries, vibration frequencies, internal rotor potentials, and thermochemical properties, ΔfHinline image, S°(T), and C°p(T) (5 K ≤ T ≤ 5000 K) were calculated at the individual B3LYP/6–31G(d,p) and the composite CBS-QB3 calculation method. The standard enthalpies of formation at 298 K were evaluated using isodesmic reaction schemes with several work reactions for each species. Entropy and heat capacities were determined using geometric parameters and frequencies from the B3LYP/6–31G(d,p) calculations for the lowest energy conformer. Internal rotor barriers were determined. Application of group additivity with comparison to calculated values is also illustrated. Transition states and kinetic parameters for intramolecular hydrogen atom transfer and molecular elimination channels were characterized to evaluate reaction paths and kinetics. Kinetic parameters were determined versus pressure and temperature for the chemical activated formation and unimolecular dissociation of the peroxide adduct. Multifrequency quantum Rice–Ramsperger–Kassel analysis was used for k(E) with master equation analysis for falloff. The kinetic analysis shows that the main reaction channels are the formation of isooctene ((CH3)3CCH=C(CH3)2) + HO2, and the formation of the cyclic: (CH3)2-y(CCH2CHO)-(CH3)2, (CH3)3C-y(CHCO)-(CH3)2, and (CH3)3C-y(CHCHCH2O)-(CH3).