['Rheumatoid factor (RF) is prototypic for rheumatoid arthritis (RA) and serves diagnostic and prognostic purposes. RF is associated with joint destruction, but the role of disease activity as a potential mediator of these effects has not been clearly elucidated yet.', 'To investigate if higher radiographic progression (Sharp score, ΔTSS) in RF+ patients is dependent or independent of disease activity.', 'The authors performed a cross-sectional multivariate analysis at baseline and a matched cohort study in patients from five RA clinical trials. The authors pooled methotrexate treatment arms and compared ΔTSS in RF+ and RF- patients before and after matching for other associated variables.', 'Among 686 patients, 124 were RF- and 562 RF+, 343 having high (>160 U/ml) RF. ΔTSS was 1.03±5.83, 3.23±8.10 and 3.58±8.18 (p<0.0001), respectively, and similarly for erosions and joint space narrowing (JSN). After matching for other prognostically important variables, ΔTSS still was lower among 61 RF- versus 61 RF high+ patients (0.52±2.47 vs 3.09±8.28; p=0.028), mainly related to differences in erosion score (0.31±1.88 vs 2.07±5.62; p=0.035), but not JSN (0.21±1.26 vs 1.02±3.31; p=0.162).'] Does rheumatoid factor determine structural progression of rheumatoid arthritis dependent and independent of disease activity?