BACKGROUND: Adult childhood cancer survivors report high levels of unemployment, although it is unknown whether this is because of health or employability limitations. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Childhood cancer survivors have higher levels of unemployment because of health or being between jobs. High-risk survivors may need vocational assistance.