Background Anti-Mi-2 antibody is a type of myositis-specific autoantibody found in idiopathic inflammatory myopathy patients. Objectives To investigate the clinical features and long-term outcomes in anti-Mi-2-positive dermatomyositis (DM) patients. Materials and Methods Serum anti-Mi-2 beta antibodies were detected in 357 DM patients by enzyme-linked immunosorbent assays, and possible associated clinical features were investigated based on cross-sectional and longitudinal studies. Results Of the DM patients, 40/357 (11.2%) were positive for anti-Mi-2 beta antibodies and found to have a significantly higher frequency of V sign (72.5% vs 45.7%;p= 0.001), shawl sign (60.0% vs 35.6%;p= 0.003), and muscle weakness (77.5% vs 57.1%;p= 0.013), but a lower incidence of interstitial lung disease (ILD) (37.5% vs 60.9%;p= 0.005) and malignancy (0% vs 12.0%;p= 0.041) than anti-Mi-2 beta-negative patients. Anti-Mi-2 beta antibody levels positively correlated with disease activity. After a median follow-up period of 44 months, 97.0% of patients showed clinical remission. Twenty-six anti-Mi-2 beta-positive patients had a disease course longer than two years, and 16/26 (61.5%) were monocyclic without relapse. Moreover, five patients (15.1%) were drug-free with complete remission for more than three months. Kaplan-Meier survival curves showed that DM patients with positive anti-Mi-2 beta had a significantly lower mortality rate compared to anti-Mi-2 beta-negative patients (log-rank;p= 0.035). Interestingly, anti-Mi-2 beta antibodies did not disappear in all patients over time. Conclusion Anti-Mi-2 beta antibodies were associated with a subgroup of DM with a low frequency of ILD and malignancy, good treatment response, and favourable outcome. Moreover, anti-Mi-2 beta levels correlated with disease activity.