Pd-based core-shell alloy-supported catalysts were prepared sequentially via a microwave-assisted polyol method and galvanic replacement. To investigate the effect of the core composition on the catalytic activity of such catalysts, three different Pd alloy cores (PdNi, PdCu, and PdNiCu) were prepared on carbon supports using a polyol method. Then, Pd and Er were introduced simultaneously to form shells on the Pd alloy cores by galvanic replacement in aqueous solution, thereby producing catalysts designated as PdNi@PdIr/C, PdCu@PdIr/C, and PdNiCu@PdIr/C. X-ray diffraction revealed that all three catalysts exhibited the face-centered cubic structure of Pd without the presence of individual phases for Ni, Cu, and Ir. The core-shell structure of the Pd-based alloy nanoparticles on the carbon support was verified by the electron energy loss spectroscopy line profile of a 25 nm nanoparticle of PdNiCu@PdIr/C. Among the three Pd-based core-shell catalysts, the highest electrochemical surface area and oxygen reduction reaction (ORR) activity was observed for PdNiCu@PdIr/C. In addition, the membrane electrode assembly employing the PdNiCu@PdIr/C catalyst displayed a significantly improved voltage compared to the other two catalysts under high-temperature polymer electrolyte membrane fuel cell conditions at 150 degrees C. Single-cell durability tests conducted to measure the voltage change at a constant current density of 0.2 A cm(-2) showed a decay ratio of 12.3 V h(-1). These results suggest that the composition of the core in core-shell nanoparticles has an important influence on both the electronic properties in the Pd alloy core and compressive lattice strain on the PdIr shell. Control of these synergistic effects provides a new approach for developing catalysts with high ORR activity.