Objectives: Treatment of connective tissue disease-related interstitial lung disease (CTD-ILD) remains challenging. The literature related to the immunosuppressive drugs is very limited in most CTDs and there is no previously reported study comparing induction regimens in patients with newly defined ‘interstitial pneumonia with autoimmune features (IPAF), We aimed to investigate the efficacy of azathioprine (AZA) used in induction regimens for interstitial lung disease in a variety of connective tissue disorders including IPAF, and compare it with cyclophosphamide (CYC) Methods. In a retrospective study, all patients presented with interstitial lung disease to the rheumatology and/or pulmonology departments in a tertiary referral centre, between 2009 and 2019. Five major CTD groups were defined; systemic sclerosis, rheumatoid arthritis (RA), primary Sjögren syndrome (pSS), inflammatory myositis (IMS) and interstitial pneumonia with autoimmune features (IPAF). All patients who satisfied one of these and received AZA or CYC for induction therapy for at least 6 months were included in the study. Treatment responses at six months and side effects were analyzed. Results: There were 1351 patients diagnosed with ILD. Of these, 328 patients were identified as CTD-ILD, satisfying the classification criteria of one of the CTDs. Among these, 57 patients received AZA and 79 patients received CYC for induction therapy. CYC treatment resulted in a 2.41 % increase in FVC, however, AZA resulted in a 1.44% decline in FVC predicted (p=0.041). Propensity score matching was used to reduce selection bias, AZA treatment was related to increased risk of progression (50% vs 13.5%, p:0.002). Conclusion: CYC is superior to AZA in induction therapy of CTD-ILD.