We compared the validity of the American College of Rheumatology (ACR) and the European League of Associations for Rheumatology (EULAR) definitions of response in rheumatoid arthritis (RA) clinical trials. US: ACR and EULAR improvement criteria were calculated in 7 large randomized RA clinical trials. The discriminant validity of the response criteria between treatment groups was studied using the Mantel-Haenszel chi-squared value. To compare both sets of criteria the chi-squared ratio was determined for each trial. Europe: In 2 large randomized RA clinical trials, ACR and EULAR criteria were calculated, once with extensive and once with 28 joint counts. The classification of patients with these 4 criteria were compared with each other using cross tables. We further studied the difference in response between treatment groups per trial, the association of response with patient and investigator assessment of improvement, and the association of response with radiological progression. US: The chi-squared ratio for most trials was close to 1. There was no clear pattern suggesting that the discriminant validity of the ACR criteria was stronger than the discriminant validity of the EULAR definition of response or vice versa. Europe: Conflicting results between ACR and EULAR were present in only 3% of patients in both trials. The discriminant validity of all 4 criteria (ACR and EULAR with reduced and extensive joint counts) was comparable. All criteria were related with the overall assessment of improvement by both investigator and patient. The association with radiographic progression was comparable for EULAR and ACR improvement criteria. There is a high level of agreement between ACR and EULAR improvement classification, and their validity is equivalent. The discriminating potential of the criteria between treatment groups is comparable, as is the association with patient's and investigator's overall assessment and with radiographic progression.