The disease activity score of 28 joints (DAS28) is now commonly used for the guidance of treatment decisions in rheumatoid arthritis (RA). The goal of this work was to determine whether patients with DAS28 > 3.2 but less than 2 swollen and 2 tender joints respond differently to treatment than patients with a higher number of active joints. One hundred and ninety two patients with active RA treated in a rheumatology hospital as in-patients were studied prospectively. At admission (T1), release (T2) and 3 months after release (T3) disease activity (DAS28-CRP at T1 + 2, RADAI at T1 + 3), pain (numeric scale at T1 - 3) and function (FFbH at T1 + 3) were measured. A total of 148 patients had two or more (group 1) and 44 less than 2 swollen and tender joints at admission (group 2) but both groups had similar over all DAS28-scores. The groups significantly differed in their outcome after 3 months: group 1 had a significant better reduction of disease activity, pain and functional deficit (p < 0.001 for the fulfilment of defined response criteria and p < 0.05 for comparison of the mean values for pain and function) in comparison to group 2. Although the numbers were small sub-analysis suggested that the differences might be due to a better response to newly administered DMARD and TNF-alpha-inhibitor therapy in group 1. Active RA patients with less than 2 swollen and 2 tender joints represent a subgroup with lower response to treatment with DMARD or TNF-alpha-inhibitors. This has to be taken into account in the management of these patients.