This paper aims to examine the interchangeability of the disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) and DAS28-CRP scores in a diverse sample of rheumatoid arthritis (RA) patients and to evaluate generalizability over gender, age, and disease duration. A sample of 682 patients was drawn from the DREAM registry. Agreement between the two DAS28 scores was analyzed using the intraclass correlation coefficient (ICC), Bland Altman plots, and a matrix of classification agreement over DAS28 disease activity categories. Despite a strong linear correlation between the DAS28 scores and a high ICC value of 0.931, a considerable lack of individual agreement could be observed, with Bland-Altman 95 % limits of agreement ranging between -0.85 and +1.25 points. On average, DAS28-CRP scores were 0.20 points lower than DAS28-ESR scores, and data stratification on age and gender showed that this systematic bias was most severe in older women (0.39 points). The overall classification agreement across DAS28 categories was 76.69 %, with the agreement being lowest (35.37 %) in the low disease activity group. Patients were more easily classified as being in remission when using the DAS28-CRP measure. DAS28-ESR and DAS28-CRP scores are not interchangeable within individuals. The DAS28-CRP tends to yield lower values of disease activity than the DAS28-ESR, resulting in substantial classification differences.