It has been shown that as concrete strength increases, the size effect becomes more pronounced in both samples and members. However, the effect of section size on the seismic performance of high-strength reinforced concrete columns requires further confirmation. For this purpose, six high-strength reinforced concrete columns were subjected to monotonic and cyclic loading in this study. The experimental results indicate that the relative nominal flexural strength, average energy dissipation coefficient, factor of safety, and local factor of safety all exhibited a strong size effect by decreasing as the column size increased. Moreover, the size effect on the factor of safety was stronger for high-strength columns than for conventional columns. The observed changes in the factor of safety were in good agreement with the Type 2 size effect model proposed by Bažant; so, using the local factor of safety and Bažant’s Type 2 model, the code equation for moment capacity was modified to provide a constant factor of safety regardless of column size.