Objective: Clostridium difficile infection (CDI) is affected by various factors. The association between CDI and antibiotic use is well known, and proton pump inhibitors (PPI) and histamine H2 receptor antagonist (H2RA) are also considered to be causative agents. The Korea Institute of Drug Safety and Risk Management has established the Medical record Observation and Assessment for drug safety Network (MOA-Net) using the common data model (CDM). We analyzed the risk factors of CDI in patients using multi-institutional hospital medical records obtained through the MOA-Net. Methods: We conducted a nested case-control study for CDI patients. Each case of CDI was matched with four controls without CDI and adjusted for sex, age, and the admission period. Patients were considered to have CDI if the disease code (A047) was present in their medical records, or if they had any clostridium difficile tests. Comorbidities, laboratory values, and the use and duration of PPI and H2RA were included in the analysis. Results: A total of 3,782 patients and 15,128 matched controls were enrolled in six participating hospitals. The occurrence of CDI was associated with the use of PPI (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.02-1.43) and H2RA (OR 2.18, 95% CI 1.85-2.56). Conditional logistic regression analyses showed that longer antibiotic use, H2RAs, a history of renal disease, decreased levels of albumin and platelets, and leukocytosis were related to CDI occurrence. Conclusion: Our study identified risk factors for CDI in Korean inpatients. We showed that analysis using multi-institutional electronic medical records through the CDM and MOA-Net is feasible.