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State-of-the-art chemistry-climate models (CCMs) have indicated that a future decrease in ozone-depleting substances (ODSs) combined with an increase in greenhouse gases (GHGs) would increase the column ozone amount in most regions except the tropics and Antarctic. However, large Arctic ozone losses have occurred at a frequency of approximately once per decade since the 1990s (1997, 2011 and 2020), despite the ODS concentration peaking in the mid-1990s. To understand this, CCMs were used to conduct 24 experiments with ODS and GHG concentrations set based on predicted values for future years; each experiment consisted of 500-member ensembles. The 50 ensemble members with the lowest column ozone in the mid- and high latitudes of the Northern Hemisphere showed a clear ODS dependence associated with low temperatures and a strong westerly zonal mean zonal wind. Even with high GHG concentrations, several ensemble members showed extremely low spring column ozone in the Arctic when ODS concentration remained above the 1980-1985 level. Hence, ODS concentrations should be reduced to avoid large ozone losses in the presence of a stable Arctic polar vortex. The average of the lowest 50 members indicates that GHG increase towards the end of the twenty-first century will not cause worse Arctic ozone depletion., (© 2023. The Author(s).)