OBJECTIVES:  To assess the health care costs, 30-day readmission rates, and predictors of 30-day readmission among patients diagnosed with clostridium difficile infection (CDI) in the US Veterans Health Administration (VHA) population (01OCT2010-30SEP2015). METHODS:  Patients diagnosed with CDI were identified (International Classification of Disease, 9^th Revision, Clinical Modification code: 008.45) from the VHA dataset for the identification period (01OCT2011-30SEPT2014). The initial diagnosis date was designated as the index date. Patients without a CDI diagnosis, who were of the same age, race, and sex as study CDI patients, were identified for comparison. An index date was randomly selected to minimize bias. Adult patients were required to have continuous medical and pharmacy benefits for 1 year pre- and post-index date. Health care costs and 30-day readmission rates during the follow-up period were compared among 1:1 matched patients with and without CDI. Logistic regression was used to examine the predictors of 30-day readmission. RESULTS:  After matching, there were 18,794 patients in each group. Patients with CDI had higher 30-day readmission rates (25.9% vs 0.6%, p<0.0001) and incurred significantly higher inpatient ($73,937 vs $892; p<0.0001), outpatient ($9,168 vs $2,035; p<0.0001) and total costs ($83,106 vs $2,928; p<0.0001) than those without CDI. The likelihood of 30-day readmission was lower among patients aged 26-34 years as compared to those aged ≥65 years (odds ratio [OR]: 0.5; p=0.0002). Readmission was higher among patients with higher mean Charlson Comorbidity Index (CCI) scores (OR: 1.1; p<0.0001). CONCLUSIONS:  Patients with CDI had a significantly higher economic burden and 30-day readmission rates than those without CDI. Age and CCI scores were significant predictors of 30-day readmission.