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Small size at birth is associated with subsequent cardiovascular disease and diabetes, and large size is associated with obesity and cancer. The overall impact of these opposing effects on mortality throughout the lifespan is unclear because causes of death change with age.We investigated the association of birth weight with adult all-cause mortality using a Danish school-based cohort of 216,464 men and women born from 1936 through 1979. The cohort was linked to vital statistic registers. The main outcome was all-cause mortality from ages 25 through 68 years. Associations with death from cancer, circulatory disease, and all other causes were also examined.During 5,205,477 person-years of follow-up, 11,149 deaths occurred among men and 6609 among women. The cumulative hazard ratios of the association between birth weight categories and all-cause mortality was constant for all ages investigated and did not differ between men and women. Compared with subjects having birth weights in the reference category (3251–3750 g), those with the lowest birth weights (2000–2750 g) had 17% higher mortality (95% confidence interval = 1.11–1.22), and those with the highest birth weights (4251–5500 g) had 7% higher mortality (1.01–1.15) from all causes. The association of birth weight with cancer increased linearly, whereas the association of birth weight with circulatory disease and all other causes was U-shaped.To the degree that the association of birth weight with adult survival is causal, the U-shaped association between birth weight and adult mortality suggests that population increases in birth weight may not necessarily lead to improved health in adulthood.