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Adult childhood cancer survivors report high levels of unemployment, although it is unknown whether this is because of health or employability limitations.We examined 2 employment outcomes from 2003 in the Childhood Cancer Survivor Study (CCSS): (1) health-related unemployment and (2) unemployed but seeking work. We compared survivors with a nearest-age CCSS sibling cohort and examined demographic and treatment-related risk groups for each outcome.We studied 6339 survivors and 1967 siblings ≥25 years of age excluding those unemployed by choice. Multivariable generalized linear models evaluated whether survivors were more likely to be unemployed than siblings and whether certain survivors were at a higher risk for unemployment.Survivors (10.4%) reported health-related unemployment more often than siblings (1.8%; Relative Risk [RR], 6.07; 95% Confidence Interval [CI], 4.32–8.53). Survivors (5.7%) were more likely to report being unemployed but seeking work than siblings (2.7%; RR, 1.90; 95% CI, 1.43–2.54). Health-related unemployment was more common in female survivors than males (Odds Ratio [OR], 1.73; 95% CI, 1.43–2.08). Cranial radiotherapy doses ≥25 Gy were associated with higher odds of unemployment (health-related: OR, 3.47; 95% CI, 2.54–4.74; seeking work: OR, 1.77; 95% CI, 1.15–2.71). Unemployed survivors reported higher levels of poor physical functioning than employed survivors, and had lower education and income and were more likely to be publicly insured than unemployed siblings.Childhood cancer survivors have higher levels of unemployment because of health or being between jobs. High-risk survivors may need vocational assistance.