Purpose There is growing awareness that the employer plays an important role in preventing early labor market exit of workers with poor health. This systematic review aims to explore the employer characteristics associated with work participation of workers with disabilities. An interdisciplinary approach was used to capture relevant characteristics at all organizational levels. Methods To identify relevant longitudinal observational studies, a systematic literature search was conducted in PubMed, Web of Science, PsycINFO and EconLit. Three key concepts were central to the search: (a) employer characteristics, (b) work participation, including continued employment, return to work and long-term work disability, and (c) chronic diseases. Results The search strategy resulted in 4456 articles. In total 50 articles met the inclusion criteria. We found 14 determinants clustered in four domains: work accommodations, social support, organizational culture and company characteristics. On supervisor level, strong evidence was found for an association between work accommodations and continued employment and return to work. Moderate evidence was found for an association between social support and return to work. On higher organizational level, weak evidence was found for an association between organizational culture and return to work. Inconsistent evidence was found for an association between company characteristics and the three work outcomes. Conclusions Our review indicates the importance of different employer efforts for work participation of workers with disabilities. Workplace programs aimed at facilitating work accommodations and supervisor support can contribute to the prevention of early labor market exit of workers with poor health. Further research is needed on the influence of organizational culture and company characteristics on work participation.