Purpose The aim of this study was to gain insight into differences and similarities in factors important for work participation in older (58-65 years) workers among three different chronic diseases: depression (D), cardiovascular disease (C), and osteoarthritis (O). Methods A mixed method design was used, with a qualitative part (in-depth interviews) with 14 patients with D, C or O and a quantitative part based on the 2002-2003 cohort of the Longitudinal Aging Study Amsterdam. We analysed and compared 3-year (response 93 %) predictors of paid work in 239 participants with D, C, or O using regression analyses. The qualitative findings were integrated with the quantitative findings aiming at complementarity. Results Common factors important for work participation were: working at baseline; male gender; lower age; partner with paid work; better physical and mental health; and higher mastery scores. The qualitative analyses added autonomy in work and provided contextual information regarding the perceived importance of working as factors important for participation in paid work. For D and C, work gave purpose in life and enhanced social contacts. Participation in work was perceived as necessary to structure life only for D. Conclusion Most factors important for work participation were similar for D, C, and O. However, the interviews revealed that for D, the context and the meaning attributed to these factors differed.