BACKGROUND: Objective measures on parental distress after a child’s cancer diagnosis are sparse. We examined the risk for first prescription of psychotropic medicine among parents of children with cancer compared with parents of children who were cancer free. In addition, we examined if sociodemographic and clinical characteristics are associated with risk of first prescription of psychotropic medication in parents of children with cancer. METHODS: We followed all parents of children with cancer (N = 6744) from the Danish Cancer Registry (1998–2014) using parents of matched children who were cancer free (N = 65 747) as a comparison. To identify vulnerable subgroups among parents of children with cancer, we followed all parents of children with cancer from the Childhood Cancer Registry (2003–2015; N = 3290 parents). In Cox proportional hazard models, we estimated hazard ratios (HRs) for a first prescription of psychotropic medication according to cancer status of the child and sociodemographic and clinical risk factors. RESULTS: Parents of children with cancer were at increased risk for a first prescription of psychotropic medication compared with parents of children who were cancer free up to 2 years after the diagnosis, the risk being highest in the first year (HR, 1.83 [95% confidence interval (CI), 1.66–2.01]). Parents of children with cancer, especially parents who lost their child, had an increased risk for a first prescription of hypnotics (HR, 6.91; 95% CI, 3.50–13.66) and anxiolytics (HR, 4.55, 95% CI, 1.57–13.17) in the first year after diagnosis. CONCLUSIONS: Efforts should be made to ensure that medical teams are adequately educated to address stress responses in the parents.