A detailed chemical kinetic model for oxidation of acetylene at intermediate temperatures and high pressure has been developed and evaluated experimentally. The rate coefficients for the reactions of C2H2 with HO2 and O2 were investigated, based on the recent analysis of the potential energy diagram for C2H3 + O2 by Goldsmith et al. and on new ab initio calculations, respectively. The C2H2 + HO2 reaction involves nine pressure- and temperature-dependent product channels, with formation of triplet CHCHO being dominant under most conditions. The barrier to reaction for C2H2 + O2 was found to be more than 50 kcal mol−1 and predictions of the initiation temperature were not sensitive to this reaction. Experiments were conducted with C2H2/O2 mixtures highly diluted in N2 in a high-pressure flow reactor at 600–900 K and 60 bar, varying the reaction stoichiometry from very lean to fuel-rich conditions. Model predictions were generally in satisfactory agreement with the experimental data. Under the investigated conditions, the oxidation pathways for C2H2 are more complex than those prevailing at higher temperatures and lower pressures. Acetylene is mostly consumed by recombination with H to form vinyl (reducing conditions) or with OH to form a CHCHOH adduct (stoichiometric to lean conditions). Both C2H3 and CHCHOH then react primarily with O2. The CHCHOH + O2 reaction leads to formation of significant amounts of glyoxal (OCHCHO) and formic acid (HOCHO), and the oxidation chemistry of these intermediates is important for the overall reaction.