Objectives The number of workers with cancer has dramatically increasing worldwide. One of the main priorities is to preserve their quality of life and the sustainability of social security systems. We have carried out this study to assess factors associated with the ability to work after cancer. Such insight should help with the planning of rehabilitation needs and tailored programmes. Participants We conducted this register-based cohort study using individual data from the Belgian Disability Insurance. Data on 15 543 socially insured Belgian people who entered into the long-term work disability between 2007 and 2011 due to cancer were used. Primary and secondary outcome measures We estimated the duration of work disability using Kaplan-Meier and the cause-specific cumulative incidence of ability to work stratified by age, gender, occupational class and year of entering the work disability system for 11 cancer sites using the Fine and Gray model allowing for competing risks. Results The overall median time of work disability was 1.59 years (95% CI 1.52 to 1.66), ranging from 0.75 to 4.98 years. By the end of follow-up, more than one-third of the disabled cancer survivors were able to work (35%). While a large proportion of the women were able to work at the end of follow-up, the men who were able to work could do so sooner. Being women, white collar, young and having haematological, male genital or breast cancers were factors with the bestlikelihood to be able to return to work. Conclusion Good prognostic factors for the ability to work were youth, woman, white collar and having breast, male genital or haematological cancers. Reviewing our results together with the cancer incidence predictions up to 2025 offers a high value for social security and rehabilitation planning and for ascertaining patients’ perspectives.