Background: Insight into how early parental death impact psychological well-being in children and young adults is important to developing suitable supportive care. The purpose of this study was to investigate the association between early parental death before the child reaches age 30 years and subsequent use of antidepressants. Methods: Our nationwide population-based cohort of persons born in Denmark in 1970-1990 with follow-up in the period 1997-2009 comprised 1,124,215 persons, of whom 71,380 were bereaved. We used Poisson models to assess rate ratios for use of antidepressants according to early parental death. Results: Follow-up yielded 13,074,146 person-years at risk during which 93,347 persons used antidepressants. Persons who experienced early parental death had an increased risk for use of antidepressants (men: risk ratio, 1.21; 95% confidence interval, 1.16, 1.26; women: 1.23; 95% confidence interval, 1.19, 1.27). We observed stronger associations for women whose parent died by suicide than from other causes, who lost their mother rather than their father, and who lost a parent early rather than later. The increased risk remained more than 2 years from the loss. Conclusions: Persons who lost a parent had an increased risk of use of antidepressants. Subgroups with particularly increased risk, included women, who were bereaved by suicides, who experienced loss of a mother, and who were bereaved when young. The risk of initiating antidepressant use was increased both immediately after the loss and later. Our results support that early parental death severely affects children's psychological well-being.