We assessed the contribution of four baseline markers-HLA-DRB1 shared epitope (SE), -308 tumor necrosis factor α gene promoter polymorphism, rheumatoid factor, and anticitrullinated peptide antibodies-for predicting persistent activity (DAS28 score ≥2.6) after one year of followup in a cohort of 201 patients with recent-onset rheumatoid arthritis (RA) or undifferentiated arthritis (UA) aged 16 years or older who had a 4-week to 12-month history of swelling of at least two joints. Patients had not been previously treated with corticosteroids or disease-modifying antirheumatic drugs (DMARD). In the best logistic regression model, only two variables were retained: SE positivity and number of DMARD administered (area under the curve = 76.4%; 95% CI: 69.2%, 84.4%; P < 0.001). The best linear regression model also included these two variables, explaining only 22.5% of the variability of DAS28 score. In this study, given an equal number of DMARD administered, the probability of persistent activity in patients with recent-onset RA or UA was significantly influenced by SE presence.