OBJECTIVES: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of hospitalizations in older adults, and comorbidities are known as a major contributing cause. Here we explore the prevalence of comorbidities and their impact on 30-day hospital readmission rates using Electronic Health Record (EHR) data to gain insight on preventing COPD-related rehospitalizations. METHODS: COPD patient records were extracted from a de-identified Cerner HealthFacts® EHR database (ICD-9 491, 492, 496), and comorbidities were analyzed according to the Elixhauser algorithms. Frequencies of COPD comorbidities and their associations with 30-day hospital readmission rates were analyzed in SAS using chi-squared tests and generalized linear mixed models. RESULTS: The top 5 comorbidities in prevalence were hypertension (46.2%), diabetes w/o chronic complications (20.0%), fluid and electrolyte disorders (15.0%), deficiency anemia (11.7%), and congestive heart failure (11.0%). 74.0% of COPD patients had at least 1 comorbidity, and 31.6% had 3 or more comorbidities. After adjusting for health systems, hospitals, and patient demographics, all of the 28 comorbidities were found to significantly increase 30-day readmission (P<0.0004 for all comorbidities). Number of comorbidities had a critical impact on 30-day readmission (P<0.0001). For example, the odds of 30-day readmission increased 6.6 times for patients with 3 comorbidities and 11 times for 5 comorbidities as compared to no comorbidity.  Overall 30-day readmission rates have decreased from 11.4% in 2001 to 5.2% in 2015. After adjusting for other factors, year of visit showed significant effect (P<0.0001). The odds of 30-day readmission decreased to 0.5 in 2015 as compared to 2001. CONCLUSIONS: COPD comorbidities significantly affect 30-day hospital readmission rates; therefore, effectively managing these comorbidities is essential for reducing COPD-related rehospitalizations. Detailed analysis of the EHR readmission data may help to evaluate the efficiency of health care management and prevent hospital readmission penalties.