To analyse if predictors of radiographic progression differ between patients treated with or without prednisolone in early rheumatoid arthritis (RA). Radiographs of hands and feet were assessed using the modified Sharp/van der Heijde score and radiographic progression was defined as an increase in the total Sharp score above 5.8 (the smallest detectable change).Prospective, randomised study of patients with early RA.Secondary level of care; six participating centres from southern Sweden; both urban and rural populations.In all, 225 patients, 64% women, with a diagnosis of RA according to the American College of Rheumatology criteria, were included if they were between 18 and 80?years of age and had a disease duration of less than 1?year.The patients were randomised to 7.5?mg prednisolone daily for 2?years (P-group; n=108) or no prednisolone (NoP-group; n=117) when they started with their first disease-modifying anti-rheumatic drug and were prospectively followed for 2?years.The frequency of patients with radiographic progression after 2?years was 26% in the P-group and 39% in the NoP-group (p=0.033). Relevant interactions between treatment and rheumatoid factor (RF) (p=0.061) and between treatment and anti-cyclic citrullinated peptide 2 (anti-CCP) (p=0.096) were found. RF and anti-CCP independently predicted radiographic progression only in the NoP-group, OR (95% CI) 9.4 (2.5 to 35.2), p=0.001 and OR (95% CI) 8.7 (2.5 to 31.3), p=0.001, respectively.The presence of RF and anti-CCP predicted radiographic progression in patients not treated with prednisolone but failed to predict progression in patients treated with this drug. The data suggest that early treatment with prednisolone may modulate not only inflammation but also autoimmunity-associated pathogenetic mechanisms.ISRCTN20612367.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.