Bimetallic 15 nm Rh1−xPdxnanoparticle catalysts of five different compositions and supported on Si wafers have been synthesized, characterized using TEM, SEM, and XPS, and studied in CO oxidation by O2 in two pressure regimes: atmospheric pressure and 100–200 mTorr. The RhPd bimetallic nanocrystals exhibited similar synergetic effect of increased reaction activity at both atmospheric (760 Torr) and moderate (100–200 mTorr) pressures compared with pure Pd or Rh. The magnitude of the effect depends on the relative pressures of the CO and O2 reactant gases and the reaction temperature. The catalytic activity of the nanocrystals measured at moderate pressure is directly correlated to the APXPS studies, which were carried out in the same pressure. The APXPS studies suggest that the Pd–Rh interfaces are important for the enhanced activity of the bimetallic nanoparticles.