Elderly patients and those with comorbid conditions are at high risk for poor outcomes after Clostridium difficile infection (CDI) but outcomes in a healthier, nonelderly population are not well described. We sought to investigate gastrointestinal diagnoses and CDI during hospitalizations in the 24 to 36 months after an initial episode of CDI in nonelderly patients in a cohort with an overall low prevalence of comorbid conditions. We performed a retrospective analysis of hospital admissions from 2010-2013 using the Truven MarketScan database of employment-based private insurance claims. Subjects <65 years of age and their adult dependents (> = 18 years old); a CDI diagnosis in 2011 (index date); at least 12 months of pre-index continuous enrollment; and 24-36 months of continuous post-index enrollment were included. The 12 months of each subject's enrollment prior to the index date for a CDI served as the reference period for the analyses of that subject's post-CDI time periods. Hospital claims during the follow-up period were evaluated for gastrointestinal diagnoses and/or CDI ICD-9 codes. The risk of gastrointestinal diagnoses was assessed using Cox proportional hazards models adjusted for a pre-specified set of baseline demographic and clinical factors. During 2011, 5,632 subjects with CDI met the inclusion criteria for our study. The risk of gastrointestinal diagnoses in patients with a CDI diagnostic code for the same admission was almost 8-fold higher 3 months post-CDI (hazard ratio (HR) = 7.56; 95% confidence interval (CI): 2.97-19.19) than for subjects without CDI and remained statistically significant until month 24 (HR = 1.47; 95% CI = 1.04-2.08). After CDI, patients remained at risk for gastrointestinal symptoms with CDI for up to two years. There is an important, long-term healthcare burden after CDI in this population.