OBJECTIVE: To describe interventions implemented during a nosocomial outbreak of Clostridium difficile in a general hospital in Costa Rica from December 2009 to April 2010 in order to achieve outbreak control and the factors determined to be associated with C. difficile infection. METHODS: Laboratory-confirmed cases of C. difficile were analyzed to describe the outbreak pattern and intervention measures implemented. Cases were selected and recruited in a case-control study. Controls were selected from the same services and time period as the cases. Evaluated exposures included underlying medical conditions and treatments administered before the onset of symptoms. RESULTS: The mean ages in case and control groups were 62.3 and 55.3 years, respectively. Control measures included a hand-hygiene campaign, deep disinfection of hospital surfaces, strict isolation of cases, use of personal protection equipment, and restriction of antibiotic use. The adjusted attributable risks associated with the outbreak were diabetes [odds ratio (OR) 3.4, 95% confidence interval (CI) 1.5-7.7], chronic renal failure (OR 9.0, 95% CI 1.5-53.0), and prescribing ceftazidime (OR 33.3, 95% CI 2.9-385.5) and cefotaxime (OR 20.4, 95% CI 6.9-60.3). CONCLUSIONS: Timely implementation of control measures resulted in reduced infection transmission and successful control of the outbreak. Conditions associated with C. difficile infection were similar to those found in previously described outbreaks of this bacterium.