Background: We aimed to examine short- and long-term mortality in a mixed population of patients with interstitial lung disease (ILD) with acute respiratory failure, and to identify those at lower vs higher risk of in-hospital death. Methods: We conducted a single-center retrospective cohort study of 126 consecutive adults with ILD admitted to an ICU for respiratory failure at a tertiary care hospital between 2010 and 2014 and who did not undergo lung transplantation during their hospitalization. We examined associations of ICU-day 1 characteristics with in-hospital and 1-year mortality, using Poisson regression, and examined survival using Kaplan-Meier curves. We created a risk score for in-hospital mortality, using a model developed with penalized regression. Results: In-hospital mortality was 66%, and 1-year mortality was 80%. Those with connective tissue disease-related ILD had better short-term and long-term mortality compared with unclassifiable ILD (adjusted relative risk, 0.6; 95% CI, 0.3-0.9; and relative risk, 0.6; 95% CI, 0.4-0.9, respectively). Our prediction model includes male sex, interstitial pulmonary fibrosis diagnosis, use of invasive mechanical ventilation and/or extracorporeal life support, no ambulation within 24 h of ICU admission, BMI, and Simplified Acute Physiology Score-II. The optimism-corrected C-statistic was 0.73, and model calibration was excellent (P =.99). In-hospital mortality rates for the low-, moderate-, and high-risk groups were 33%, 65%, and 96%, respectively. Conclusions: We created a risk score that classifies patients with ILD with acute respiratory failure from low to high risk for in-hospital mortality. The score could aid providers in counseling these patients and their families.