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This is a prospective 12 month (July 2003-June 2004) cohort study in one large tertiary hospital of Santiago, Chile aimed to describe clinic features and calculate the direct costs of hospitalization associated to community-acquired (n = 78) and nosocomially-acquired (n = 52) rotavirus infection. A gastroenteritis severity score after Rennels 1996, (0 to 17 points) was applied and costs where calculated based on those assigned by the Chilean National Funds for Health (FONASA). Severe gastroenteritis manifested by a score > 14 occurred in 26.9% and 9.6% of community and nosocomially-acquired cases respectively (p < 0.015). The former had lower bicarbonate levels (p < 0.001), and required more volume expansion compared to the latter (p < 0.023). The average cost was US 277 per case for community acquired rotavirus and US 268 for nosocomial infection. In this hospital the cost of nosocomial rotavirus infection was approximately 13,900 US dollars for a 12 month period. These results should stimulate the implementation of active prevention and control programs.