OBJECTIVE: Assessing the disease activity is a key part of clinical decision-making in rheumatology. In particular, a high disease activity, which is represented by a disease activity score-28 (DAS28) score >5.1, is used as a cutoff value for the use of biologics in many countries, including Korea. This study compared the DAS28-erythrocyte sedimentation rate (ESR) and DAS28-C-reactive protein (CRP) to determine if these indices can be used interchangeably in patients with high disease activity. METHODS: This cross-sectional study enrolled 1,117 patients with rheumatoid arthritis and examined the initial registration data from the Korean Biologics Registry. RESULTS: In general, DAS28-CRP showed an excellent correlation with DAS28-ESR (r2=0.889, p <0.001). On the other hand, DAS28-CRP tended to underestimate the disease activity in those with moderate-to-high disease activity. The best agreement between DAS28-ESR and DAS28-CRP for defining a high disease activity was achieved using a cutoff value of 4.5 for the latter (kappa, 0.68; sensitivity, 85.9%; specificity, 88.1%). CONCLUSION: DAS28-CRP correlates well with DAS28-ESR; however, the cutoff value of the former needs to be reduced to 4.5 if these two indices are to be used interchangeably to define a high disease activity.