Carbon-supported octahedral Pt-Ni nanoparticles (oct-Pt-Ni/C) have been expected to be one of the most promising cathode catalysts for polymer electrolyte membrane fuel cells because of their extremely high catalytic activities for oxygen reduction reaction. While the effects of the Pt-Ni composition and the particle size on the activity have been widely studied to achieve the highest activity, their effects on the durability have been hardly examined. Here, we synthesized oct-Pt-Ni/C with different Pt-Ni compositions and sizes by changing concentrations of the precursors and the protecting agents, respectively. Then, their degradation behaviors were systematically examined by using an RDE-based accelerated durability test (ADT). Although the oct-Pt-Ni/C exhibited extremely high activities (630–3400 A g−1-Pt) with a volcano-like dependency against the Ni atomic ratio, all these ORR activities rapidly decreased in the beginning to approach that of Pt/C (400 A g−1-Pt). After the ADT, all the oct-Pt-Ni/C lost their octahedral shape through Ni leaching. There was no significant dependency of the degradation rate on the Pt-Ni composition and the particle size for the oct-Pt-Ni/C with the sizes smaller than 7 nm, which are needed to exhibit at least decent performances in a fuel cell. Therefore, further efforts are needed to develop highly durable oct-Pt-Ni/C.