During the past few decades age at death for individuals with Down syndrome (DS) has increased dramatically. The birth frequency of infants with DS has long been constant in Sweden. Thus, the prevalence of DS in the population is increasing. The aim of the present study was to analyze mortality and causes of death in individuals with DS during the period 1969–2003. All individuals with DS that died between 1969 and 2003 in Sweden, and all individuals born with DS in Sweden between 1974 and 2003 were included. Data were obtained from the Swedish Medical Birth Register, the Swedish Birth Defects Register, and the National Cause of Death Register. Median age at death has increased by 1.8 years per year. The main cause of death was pneumonia. Death from congenital heart defects decreased. Death from atherosclerosis was rare but more frequent than reported previously. Dementia was not reported in any subjects with DS before 40 years of age, but was a main or contributing cause of death in 30% of the older subjects. Except for childhood leukemia, cancer as a cause of death was rare in all age groups. Mortality in DS, particularly infant mortality, has decreased markedly during the past decades. Median age at death is increasing and is now almost 60 years. Death from cancer is rare in DS, but death from dementia is common. © 2013 Wiley Periodicals, Inc.