Objective. Heterogeneity exists among patients with myositis who have antinuclear matrix protein 2 (anti-NXP2) antibodies, although they usually present with severe muscle weakness. 'This study aimed to investigate the differences in phenotypes and prognoses among adult patients with myositis who have anti-NXP2 antibodies. Methods. Adult patients with myositis who have anti-NXP2 antibodies were enrolled from January 2010 to December 2019.1 heir clinical features and laboratory data were recorded retrospectively. We followed up on their survival status until June 30, 2020. A hierarchical cluster analysis, Kaplan-Meier curves, and classification and regression trees were used to analyze the data. Results. A total of 70 adult patients with myositis who have anti-NXP2 antibodies were enrolled. All patients experienced muscle weakness. A total of 11 patients did not present with rashes during disease progression, and 43 patients developed dysphagia. In total, 21 patients had interstitial lung disease (ILD), whereas no patients had rapidly progressive ILD. Hierarchical cluster analysis identified 2 clusters. Patients in duster 1 were younger at disease onset, had a higher incidence of subcutaneous calcification, and had a lower incidence of V sign and shawl sign. Patients in cluster 2 had a higher frequency of ILD, accompanied by lower levels of lymphocytes and higher levels of serum ferritin. Moreover, patients in duster 2 had worse prognoses. Conclusion. Patients with myositis who have anti-NXP2 antibodies may present with different phenotypes that arc characterized by unique features and prognoses.