A range of late effects is associated with the survival of childhood cancer, including problems with employment. The purpose of this metaanalysis was to assess the risk of unemployment of adult survivors of childhood cancer compared with healthy controls and to explore prognostic factors. A literature search of studies published between 1966 and January 2006 was conducted using the databases of MedLine, CINAHL, EMBASE, ClinPSYCH, PsycINFO, and OSHROM. The authors synthesized data using a random effects model. A total of 34 articles was found, in which 40 original empirical studies were reported, 24 of which were controlled studies. Survivors of childhood cancer were nearly twice as likely to be unemployed than healthy controls (odds ratio [OR] 1.85, 95% confidence interval [95% CI], 1.27-2.69). Survivors of central nervous system (CNS) and brain tumors were nearly 5 times more likely to be unemployed (OR 4.74, 95% CI, 1.21-18.65), whereas the risks for survivors of blood or bone cancers were elevated but not found to be statistically significant (OR 1.42, 95% CI, 0.79-2.55; OR 1.97, 95% CI, 0.88-4.40, respectively). No increased risk was found for survivors of other or mixed diagnoses (OR 0.97, 95% CI, 0.27-3.53). Furthermore, survivors in the U.S. had an overall 3-fold risk (OR 3.24, 95% CI, 2.16-4.86) of becoming unemployed, whereas no such risk was found for European survivors (OR 1.00, 95% CI, 0.58-1.70). Apart from type of diagnosis and country, predictors of unemployment were younger age, lower education or intelligence quotient, female gender, motor impairment or epilepsy, and radiotherapy. Adult survivors of childhood cancer are at risk of unemployment, especially the subgroup of survivors of CNS and brain tumors. Interventions to enhance participation in work life should be developed and evaluated. Cancer 2006. © 2006 American Cancer Society.