The incidence and severity of Clostridium difficile infections (CDI) have increased in Western countries. However, there are limited data regarding the epidemiology of CDI in Eastern countries. This nationwide study was conducted in 17 hospitals to determine temporal trends in CDI incidence (from 2004 to 2008) in South Korea. The total incidence of CDI in Korea was 1·7 cases/1000 adult admissions in 2004, and 2·7/1000 cases in 2008 (P = 0·028). When analysing the clinical features of 1367 CDI patients diagnosed in 2008, oral metronidazole was effective as a first-line treatment for CDI (61·9%). Relapse rate was 8·9% and complicated CDI was only observed in 3·6%. The incidence of CDI increased significantly in Korea from 2004 to 2008. Although the clinical features were milder than in Western countries, the increasing burden of CDI needs ongoing surveillance systems.