Objective. To evaluate and compare the utility of commonly used outcome measures for assessing disease exacerbation or flare in patients with rheumatoid arthritis (RA). Methods. Data from the Dutch Potential Optimalisation of (Expediency) and Effectiveness of Tumor necrosis factor-α blockers (POET) study, in which 462 patients discontinued their tumor necrosis factor-α inhibitor, were used. The ability of different measures to discriminate between those with and without physician-reported flare or medication escalation at the 3-month visit (T2) was evaluated by calculating effect size (ES) statistics. Responsiveness to increased disease activity was compared between measures by standardizing change scores (SCS) from baseline to the 3-month visit. Finally, the incremental validity of individual outcome measures beyond the Simplified Disease Activity Score was evaluated using logistic regression analysis. Results. The SCS were greater for disease activity indices than for any of the individual measures. The 28-joint Disease Activity Score, Clinical Disease Activity Index, and Simplified Disease Activity Index performed similarly. Pain and physician's (PGA) and patient's global assessment (PtGA) of disease activity were the most responsive individual measures. Similar results were obtained for discriminative ability, with greatest ES for disease activity indices followed by pain, PGA, and PtGA. Pain was the only measure to demonstrate incremental validity beyond SDAI in predicting 3-month flare status. Conclusion. These results support the use of composite disease activity indices, patient-reported pain and disease activity, and physician-reported disease activity for measuring disease exacerbation or identifying flares of RA. Physical function, acute-phase response, and the auxiliary measures fatigue, participation, and emotional well-being performed poorly.