This study aimed to assess the diagnostic and prognostic value of anti-mutated citrullinated vimentin (MCV) antibodies in very early rheumatoid arthritis (VERA) and in established rheumatoid arthritis (RA). Seventy-one patients with undifferentiated arthritis (UA) of <3 months duration, 141 with established RA, 53 with other rheumatic diseases, and 40 healthy individuals were included in the study. Anti-MCV, anti-cyclic citrullinated peptide (CCP) antibodies, and rheumatoid factor (RF) were determined and hand radiographs were recorded. Patients were assessed prospectively for 2 years, and hand radiographs were repeated. Diagnostic performance of anti-MCV was studied with receiver operating characteristic (ROC) curves and evaluation of sensitivity, specificity, and likelihood ratios. Forty-six percent of UA patients progressed to RA at 2 years. In VERA patients, sensitivity of anti-MCV was 52 %, compared to 44 % of anti-CCP and 37 % of RF, while specificity was 91 %, compared to 91 % of RF and 84 % of anti-CCP. Anti-MCV were detected in 25 % of VERA patients negative for both anti-CCP and RF. In established RA, anti-MCV did not sustain its diagnostic performance. By multivariable analysis, anti-MCV, but not anti-CCP or RF, showed significant correlation with radiographic progression in VERA patients. In established RA, anti-MCV, anti-CCP, and RF were associated with active disease (p ≤ 0.03) and joint damage (p ≤ 0.004). By multivariate analysis, the strongest factors for radiographic damage were disease duration (p = 0.000), HAQ score (p = 0.000), and RF (p = 0.002). In conclusion, in patients with very early UA, anti-MCV predict both progression to RA and radiological damage, and therefore, anti-MCV antibody testing may be useful in every day practice.