We have studied the thermal stability of NCM622 cathode material for Li-ion batteries using real-time synchrotron x-ray scattering below 600°C in both air and vacuum. The expansion of the mean particle size, which reached maximum values of 10.3 μm in air and 10.6 μm in vacuum at 200°C, was attributed to the dehydration of intergranular water within the NCM622 powders. Across all annealing temperatures, the amount of crystal NCM622 phase in air was consistently higher than that in vacuum. The crystal domain sizes in air showed less variation than that in vacuum during annealing from RT to 500°C. These indicate that the crystal NCM622 phase is more thermally stable during annealing in air than in vacuum. This stability is attributed to the presence of 21% oxygen in air, which is absent under vacuum conditions.