Background Inflammatory bowel disease (IBD) is associated with high costs to society. Few data on the impact of IBD on work disability and potential predictive factors are available. Aim To assess the prevalence of and predictive factors for work disability in Crohn's disease (CD) and ulcerative colitis (UC). Methods A web-based questionnaire was sent out in seven university hospitals and seven general hospitals in the Netherlands. Initially, 3050 adult IBD patients were included in this prospective, nationwide cohort study, whereof 2629 patients were within the working-age (18–64 years). We used the baseline questionnaire to assess the prevalence rates of work disability in CD and UC patients within working-age. Prevalence rates were compared with the Dutch background population using age- and sex-matched data obtained from Statistics Netherlands. Multivariable logistic regression analyses were performed to identify independent demographic- and disease-specific risk factors for work disability. Results In CD, 18.3% of patients was fully disabled and 8.8% partially disabled, compared to 9.5% and 5.4% in UC patients (p < 0.01), respectively. Compared to Dutch controls, the prevalence was significantly higher, especially in CD patients. Higher age, low education, depression, chronic back pain, joint manifestations and typical disease-related risk factors such as penetrating disease course and surgery in the past were all found to be associated with work disability. Conclusion We report high work disability rates in a large sample of IBD patients in the Netherlands. CD patients suffer more frequently from work disability than UC patients. A combination of demographic and disease-related factors is predictive of work disability.