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Inflammatory bowel disease (IBD) patients with Clostridium difficile co-infection (CDCI) have an increased risk of morbidity and mortality. We aim to evaluate the impact of CDCI on in-hospital outcomes among adults with IBD hospitalized in the USA.Using the 2007–2013 Nationwide Inpatient Sample, hospitalizations among US adults with Crohn’s disease (CD), ulcerative colitis (UC) and CDCI were identified using ICD-9 coding. Hospital charges, hospital length of stay (LOS), and in-hospital mortality was stratified by CD and UC and compared using χ2-testing and Student’s t-test. Predictors of hospital charges, LOS, and in-hospital mortality were evaluated with multivariate regression models and were adjusted for age, sex, race/ethnicity, year, insurance status, hospital characteristics, and CDCI.Among 224 500 IBD hospitalizations (174 629 CD and 49 871 UC), overall prevalence of CDCI was 1.22% in CD and 3.41% in UC. On multivariate linear regression, CDCI was associated with longer LOS among CD [coefficient: 5.30, 95% confidence interval (CI): 4.61–5.99, P<0.001] and UC (coefficient 4.08, 95% CI: 3.54–4.62, P<0.001). Higher hospital charges associated with CDCI were seen among CD (coefficient: $35 720, 95% CI: $30 041–$41 399, P<0.001) and UC (coefficient: $26 009, 95% CI: $20 970–$31 046, P<0.001). On multivariate logistic regression, CDCI was associated with greater risk of in-hospital mortality (CD: odds ratio: 2.74, 95% CI: 1.94–3.87, P<0.001; UC: OR: 5.50, 95% CI: 3.83–7.89, P<0.001).Among US adults with CD and UC related hospitalizations, CDCI is associated with significantly greater in-hospital mortality and greater healthcare utilization.