Background Return to work with or after a chronic disease is not a very well understood process, influenced by a variety of personal, professional, societal and medical factors. The aim of this study is to identify predictors for return to work 12 months after a solid organ transplant applying a bio-psycho-social model. Methods This study is based on patients included in the Swiss Transplant Cohort Study, a national prospective multicentre cohort, who underwent a first solid organ transplant (kidney, liver, heart, lung). Bio-psycho-social factors were tested and predictors of return to work identified using logistic regression models. Results Among the 636 patients included in the study, 49.8% (317) were employed 12 months post-transplant. The major predictor for returning to work 12 months posttransplant was pre-transplant employment status (OR 10.8). Accordingly, the population was stratified in employed and not employed pre-transplant groups. Age, self-perceived health (6 months post-transplant) and the transplanted organ were significantly associated with post-transplant employment status in both groups. Return to work was influenced by education, depression (6 month post-transplant) and waiting time in the employed pre-transplant group and by invalidity pension in the not employed pre-transplant group. Conclusion Employment status pre-transplant being highly associated with employment status post-transplant, the process promoting return to work should be started well before surgery. Biomedical, psychological and social factors must be taken into account to promote return to work in transplanted patients.