Abstract The high-dose glucocorticosteroid (GC) treatment is the first choice for dermatomyositis complicated with interstitial lung disease (DM-ILD) but patients are resistant to the high-dose GC monotherapy. Besides, the high dose of GC, the secondary immunosuppressive agent(s) is necessary but there is controversy for the selection of immunosuppressive agent(s). The objectives of the study were to analyze the efficacy of different therapeutic options for DM-ILD to identify the optimal therapy. A total of 60 patients had received intravenous 1.0–2.0 mg/ kg/day prednisolone for DM-ILD. In severe conditions, patients had received oral 1 to 3 mg/day tacrolimus (TAC), 500 mg/ m²/month cyclophosphamide (CY), and/or 1 g/ day methylprednisolone pulse (TI cohort, n = 24). In severe conditions, patients had received 1 g/day methylprednisolone pulse and 2–3 mg/ kg/day cyclosporine A (CsA) and/or 500 mg/ m²/month CY (existing historical treatment; CT cohort, n = 36). Patients of the TI cohort did not receive CsA. Patients in the CT cohort were received CY in significantly fewer numbers than those of the TI cohort during treatment (P = .0112). A total of 11 (46%) patients from the TI cohort and 14 (39%) patients from the CT cohort were developed relapsed. At the end of the 30-months, higher numbers of patients of the TI cohort had an event(s) free survival than those of the CT cohort (7 (29%) vs 2 (6%), P = .0229). Also, higher numbers of patients of the TI cohort had survived irrespective of an event(s) than those of the CT cohort (21 (87%) vs 22 (61%), P = .0399). Patients of the TI cohort had developed herpes zoster (2 (8%)) and cytomegalovirus (4 (17%)) infections. Patients of the CT cohort developed renal dysfunction (10 (28%)). Hyperglycemia, hyperlipidemia, and fracture (GC-related toxicities) were also reported in both cohorts and these toxicities were fever in the TI cohort. The addition of TAC to high doses GC with CY is an ideal treatment for severe conditions of DM-ILD (Level of Evidence: III; Technical Efficacy Stage: 4).