OBJECTIVE To assess plasma M-ficolin concentrations in disease-modifying antirheumatic drug (DMARD)-naive patients with early rheumatoid arthritis (RA), to investigate the correlation of M-ficolin concentrations with disease activity markers, and to determine the predictive value of M-ficolin with respect to the Disease Activity Score in 28 joints (DAS28). METHODS The study group included 180 DMARD-naive patients with early RA who participated in a randomized controlled trial of methotrexate and intraarticular glucocorticoids plus either adalimumab or placebo/adalimumab. One hundred healthy control subjects and 51 patients with chronic RA were also assessed. A sandwich-type time-resolved fluorometric immunoassay was used for quantification of plasma M-ficolin. RESULTS At baseline, M-ficolin levels were highest in the group of DMARD-naive patients with newly diagnosed active RA, and the level in these patients decreased 26% after 1 year of aggressive treatment. The baseline M-ficolin level correlated with 5 of 7 disease activity markers, including the DAS28 and the Health Assessment Questionnaire (HAQ), and a similar pattern of correlations was observed at 1 year. Multiple logistic regression analysis showed that an elevated M-ficolin level at baseline was the strongest predictor of not achieving either DAS28 remission (odds ratio [OR] 4.18, 95% confidence interval [95% CI] 2.02-8.63) or low disease activity (OR 2.45, 95% CI 1.13-5.28) at 1 year. The presence of a baseline M-ficolin level in the lowest quartile resulted in sensitivity of 29%, specificity of 93%, and positive predictive value of 95% for low disease activity at 1 year. CONCLUSION In patients with early RA, elevated plasma M-ficolin levels correlated with a high DAS28 and a high HAQ score at baseline and 1 year. A low M-ficolin level was the strongest predictor of remission and low disease activity in a multivariate analysis.