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Over the last decade a significant increase in the life expectancy of people with Down syndrome (DS) has been observed, which has caused a higher incidence of morbidity as they age. However, there is a lack of literature regarding morbidity and hospitalization of adults with DS. Analysis of 297 hospitalizations of 120 adults with DS aged 18-73 years hospitalized at Hadassah Medical Centers during the years 1988-2007 compared with data of the general population, hospitalized at the same period. At the age range 18-66 years, mean number of hospitalizations was significantly higher than the general population (P = 0.000001) with hospitalization also significantly longer (P = 0.0009). Exceptionally long hospitalizations were seen at the departments of internal medicine, dermatology and intensive care units. There was no significant difference in mortality between DS and the general population (P = 0.221). More than a fourth of the hospitalizations were caused by infectious diseases, mostly respiratory infections. Hypothyroidism was more prevalent compared with the estimated number reported by the literature (30.8% vs. 15%). Convulsive disorder was prevalent as well (15.8%). However, the prevalence of congenital heart disease, dementia, osteoporosis and obesity was found less than expected. Adults with DS are hospitalized more than the general population and for longer duration. The results of this study emphasize the need for preventive community-based medicine, awareness of co-morbidities and possible deterioration and to prepare the medical staff for a complex course of illness, expecting longer hospitalizations, arising from the complexity of this population. (Contains 7 tables.)