Objective: The serum myositis-specific autoantibodies has been considered to be relatively specific and be useful for diagnosis of polymyositis/dermatomyositis associated interstitial lung disease (PM/DM-ILD). The goal of our retrospective study was to identify clinical features and prognostic factors for PM/DM-ILD based on serological phenotypes.Methods: PM/DM-ILD patients were diagnosed in the Department of Respiratory Medicine, Nanjing Drum Tower Hospital. MSAs were measured by anti-myositis antibody profile IgG detection kit. Based on the results of MSAs, the patients were divided into three groups: anti-MDA5 group, anti-Jo-1 group and other anti-ARS group. Kaplan-Meier, log rank, Kruskal-Wallis test and chi-square tests were used for analysis.Results: We identified 30 patients (22.0%) with positive anti-MDA5, 42 patients (31.0%) with positive anti-Jo-1 and 64 patients(47.0%) with other anti-ARS. acute disease onset was more frequently observed in the anti-MDA5 group (P = 0.005). The highest mortality rate was in the anti-MDA5 group (66.7%, P < 0.001). The overall survival of patients with anti-Jo-1 was significantly better than that of patients with anti-MDA5 (P < 0.001) and similar to that of patients with other anti-ARS. The acute disease onset (P = 0.002), DAD pattern for HRCT imaging (P < 0.001), current smokers (P = 0.02), presence of Anti-MDA5 (P < 0.001), fever (P < 0.001) were significantly associated with the mortality of the study population. Interestingly, in the subgroup survival analysis for anti-MDA5 group, age was a risk factor for death of patients with anti-MDA5 (P = 0.02), and the treatment with PSL pulse and IVIG were markedly correlated with high mortality (P < 0.001 and P = 0.001, respectively).Conclusion: Anti–MDA5 antibody is significantly associated with associated with worse prognosis in PM/DM-ILD patients. The application of PSL pulse and IVIG are not necessarily an effective treatment for positive anti-MDA5 patients.