A longitudinal study has identified differences in the clinical manifestations of patients with anticitrullinated protein antibody (ACPA)-positive (n = 30) and ACPA-negative (n =37) rheumatoid arthritis (RA) during the pre-RA phase. Initial symptoms involved the lower extremities more often in the ACPA-positive group. At first presentation with arthralgia, ACPA-positive patients had a longer symptom duration, lower number of tender joints and less difficulty making a fist. However, ACPA-positive patients developed arthritis sooner after presenting with arthralgia than ACPA-positive patients.