OBJECTIVES: Several researches have led to contradictory results on the question whether there was an excess mortality rate in CDI patients. The objective of this study was to estimate the increase of mortality attributable to Clostridium difficile infection (CDI). METHODS: A French cohort of patients with a first episode of ICD hospitalized between 2007 and 2014 was extracted from a 1% representative sample of subjects covered by the general health insurance (EGB database, ≈600,000 patients). The one year incidence of deaths was estimated and compared to a control group with no CDI (2 controls per case) matched on a propensity score (PS). PS was calculated with the variables: age, gender, Charlson index, duration of stay, year of index stay and main comorbidities. A cox and a Poisson models were used to estimate the increase risk of death while adjusting on the PS. Sensitivity analyses were performed to explore the robustness of the results. RESULTS: Data from 482 ICD and 964 PS matched controls were extracted. The 2 groups were very similar when compared with the variables used to calculate the PS. Significant increase of death rates was found in CDI patients with HRs of 1.65 (CI95%=[1.33;2.04]) unadjusted and 1.58 (CI95%=[1.27;1.97]) adjusted on PS. The PS adjusted RRs were 1.78 (CI95%=[1.18;2.70]) at 28 days, 1.52 (CI95%=[1.17;1.98]) at 3 months, 1.52 (CI95%=[1.20;1.93]) at 6 months and 1.64 (CI95%=[1.32;2.03]) at 12 months. Sensitivity analyses were performed and lead to similar result : patients for whom the CDI infection was coded as the main diagnosis (HR=1.90 (CI95%=[1.27;2.86]) ; Matched controls hospitalized for a disease with diarrhea (HR=1.44 (CI95%=[1.15;1.79])) ; Patients not rehospitalized for CDI after the index stay (HR=1.73 (CI95%=[1.37;2.18])). CONCLUSIONS: CDI infection leads to a significant one year increase of death rate when compared to similar patients in terms of age, gender, comorbidities and length of stay.