BACKGROUND: Clostridium difficile infection (CDI) is associated with a substantial Quality of life impact on patients that has not been so far measured with a generic validated instrument. METHODS: A prospective study was performed in 7 French acute-care settings in patients presenting with a bacteriologically-confirmed CDI. The EQ-5D-3 L was filled in by patients at 7 +/- 2 days after CDI diagnosis to describe their state of health at that date as well as their state of health immediately before the CDI episode (baseline). Individual utility decrement was obtained by subtracting the corresponding utilities. The Quality Adjusted Life Year (QALY) loss was calculated by multiplying the days spent from baseline to the date of the interview, by the decrement of utility. A multivariate analysis of variance of the utility decrement according to CDI and patients characteristics was performed. RESULTS: Eighty patients were enrolled (mean age: 69.4 years, 55% females). The utility scores dropped from a mean 0.542 (SD: 0.391) at baseline to 0.050 (SD: 0.404) during the CDI episode with a mean adjusted utility decrement of 0.492 (SD: 0.398) point. This decrement increased significantly with CDI severity (Zar score >/= 3) (p = 0.001), in patients with a positive baseline utility (p = 0.032), in women as compared to men (p = 0.041) and in patients aged more than 65 years (p = 0.041). No association with the Charlson index was found. The associated QALY loss not integrating the excess mortality was 0.028 (SD: 0.053). CONCLUSIONS: The impact on quality of life of CDI episodes is major and translates in a substantial QALY loss despite their short duration.