Background/Objective: We have limited knowledge regarding characteristics of patients with interstitial pneumonia with autoimmune features (IPAF) that are associated with response to immunosuppression. In this study, we used published IPAF criteria to characterize features associated with response to treatment. Methods: We conducted a single-center medical records review study of 63 IPAF patients to evaluate for serological, clinical, and morphological characteristics that are associated with response to immunosuppression. Response was defined as % relative functional vital capacity decline of less than 10% and absence of death or lung transplant within the first year of continuous immunosuppressive therapy. Nonparametric measures of association and multivariate logistic regression were used to evaluate the relationship between baseline characteristics and immunosuppressive response. Results: There was a trend of greater progression among men, ever smokers, those negative for antisynthetase antibodies, and those with usual interstitial pneumonia radiographic pattern, but no statistically significant relationship was found between baseline serological, clinical, or morphological features and response to immunosuppression. Patients on combination therapy with mycophenolate mofetil and prednisone had less disease progression (p = 0.018) than those on regimens that did not include both of these medications. Conclusions: In our cohort, baseline clinical assessment did not identify which patients with IPAF will respond to immunosuppressive therapy. Combination therapy with mycophenolate mofetil and prednisone was associated with lack of disease progression in our IPAF patients, including in IPAF–usual interstitial pneumonia. Further studies are needed to evaluate which IPAF patients would benefit from immunosuppressive therapy, antifibrotic therapy, or a combination of both.