Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of hospital readmissions. Few existing tools use electronic health record (EHR) data to forecast patients’ readmission risk during index hospitalizations.

Objective: We used machine learning and in-hospital data to model 90-day risk for and cause of readmission among inpatients with acute exacerbations of COPD (AE-COPD).

Patients: Adult patients admitted for AE-COPD at the University of Chicago Medicine between November 7, 2008 and December 31, 2018 meeting International Classification of Diseases (ICD)-9 or − 10 criteria consistent with AE-COPD were included.

Methods / Measures: Random forest models were fit to predict readmission risk and respiratory-related readmission cause. Predictor variables included demographics, comorbidities, and EHR data from patients’ index hospital stays. Models were derived on 70% of observations and validated on a 30% holdout set. Performance of the readmission risk model was compared to that of the HOSPITAL score.

Results: Among 3238 patients admitted for AE-COPD, 1103 patients were readmitted within 90 days. Of the readmission causes, 61% (n = 672) were respiratory-related and COPD (n = 452) was the most common. Our readmission risk model had a significantly higher area under the receiver operating characteristic curve (AUROC) (0.69 [0.66, 0.73]) compared to the HOSPITAL score (0.63 [0.59, 0.67]; p = 0.002). The respiratory-related readmission cause model had an AUROC of 0.73 [0.68, 0.79].

Conclusions: Our models improve on current tools by predicting 90-day readmission risk and cause at the time of discharge from index admissions for AE-COPD. These models could be used to identify patients at higher risk of readmission and direct tailored post-discharge transition of care interventions that lower readmission risk.