Siblings of children with cancer experience severe stress early in life. Most studies of mental health problems in these siblings are limited by being small, cross-sectional, or self-reporting. In a population-based cohort study, we investigated the risk for antidepressant use by linking several nationwide, population-based registries comparing 6644 siblings of children diagnosed with cancer from 1991-2009 with 128 436 population-based sibling comparisons using the Cox proportional hazards model. Irrespective of cancer type, no increased risk of antidepressant use in siblings of children with cancer was found (hazard ratio = 1.00, 95% confidence interval = 0.91 to 1.11). However, data suggested that siblings being young at cancer diagnosis had an increased risk (2-sided Ptrend = .01). Interaction analyses showed no modifying effect of parental socioeconomic position or antidepressant use. Findings from this study with a very low risk of bias are reassuring and important for families facing childhood cancer and for clinicians counseling these families.