Background: Exposure to childhood out-of-home care (OHC, foster family and residential care) is associated with an increased risk of suicide in youth and young adulthood, but the life course and clinical psychiatric implications of this risk have not yet been well elucidated. Methods: This was a national cohort study generated from linkage of a range of population-based registers, resulting in a national cohort of 838 714 where 24 628 (2.9%) had a history of OHC. The study population, born 1972–1981, was followed from age 18 to age 39–48 years for suicide death and hospitalized self-harm. Results: Exposure to OHC accounted for 14% of all suicide deaths in the cohort. The age-adjusted Hazard Ratios (HRs) for exposure to OHC on suicide death were 5.04 (95% C.I. 4.50–5.64) for men and 7.21 (6.13–8.48) for women compared with the same gender in the general population. After adjusting for year of birth, childhood SES and parental morbidity these risks were attenuated to 3.39 (2.99–3.85) for men and 4.23 (3.50–5.12) for women. For hospitalized self-harm the adjusted HRs were 4.47 (4.18–4.79) for men and 4.25 (4.00–4.52) for women. These risks remained similarly high from age 18 years to 48 years. Exposure to childhood OHC carried a higher risk of suicide also among psychiatric inpatients, age-adjusted HR 1.70 (1.50–1.94). Conclusion: Exposure to OHC during childhood is a major predictor for suicide and self-harm in young and middle-aged adults as well as among adult psychiatric patients.