This paper describes the epidemiology of hospitalised cases with influenza-like illness (ILI) and laboratory-confirmed influenza A cases in Sicily (Italy) during the 2009 influenza pandemic. The first ILI case diagnosed as infected with pandemic influenza A(H1N1)2009 in Sicily was reported in June 2009 and it rapidly became the dominant circulating strain. In the period from 30 April 2009 through 31 December 2010, a total of 2,636 people in Sicily were hospitalised for ILI and 1,193 were laboratory-confirmed for influenza A. Basic demographic and clinical information for all hospitalised patients was collected and population mortality rates (PMRs) and case fatality ratios (CFRs) were calculated. The median age of hospitalised patients infected with pandemic influenza A(H1N1)2009 was significantly lower than that of hospitalised ILI cases in general (18.0 vs. 32.1 years; p<0.0001). Among adults, women were more susceptible than men. The majority of clinical presentations were mild, but 6.6% of hospitalised patients required admission to an intensive care unit, of whom 26.3% had confirmed influenza A. Twenty-four fatal cases were documented. The age group of 45–54 year-olds showed the highest PMRs once hospitalised, while CFRs were higher in elderly patients of 65 years and older. All fatal cases were confirmed as influenza A(H1N1)2009 and most of them had established risk factors for influenza complications.