Objectives To compare the presentation of seropositive and seronegative early rheumatoid arthritis (RA) in disease-modifying antirheumatic drug (DMARD)-näive patients classified according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria. Methods All patients had symptom duration from first swollen joint textless2 years and were DMARD naive with an indication for DMARD treatment. Patients were stratified as seropositive ( positive rheumatoid factor (RF)+ and/or anticitrullinated peptide antibody (ACPA)+) or seronegative (RF-and ACPA-), and disease characteristics were compared between groups. Results A total of 234 patients were included, and 36 (15.4%) were seronegative. Ultrasonography (US) scores for joints (median 55 vs 25, ptextless0.001) and tendons (median 3 vs 0, ptextless0.001), number of swollen joints (median 17 vs 8, ptextless0.001), disease activity score (DAS; mean 3.9 vs 3.4, p=0.03) and physician global assessment (mean 49.1 vs 38.9, p=0.006) were significantly higher in seronegative patients compared with seropositive. Total van der Heijde-modified Sharp score, Richie Articular Index and patient-reported outcome measures were similar between groups. Conclusions Seronegative patients had higher levels of inflammation, assessed both clinically and by US, than seropositive patients. These differences may reflect the high number of involved joints required for seronegative patients to fulfil the 2010 ACR/EULAR classification criteria for RA. Trial registration number NCT01205854; Pre-results.