INTRODUCTION: The promotion of return to work (RTW) following occupational injury benefits injured workers, their families, enterprises and the society. The identification of the potential determinants would be helpful in improving RTW rate and minimizing the duration of absenteeism following injury. OBJECTIVES: The aim of the study was to identify the potential determinants of RTW following work-related injury. METHODS: A historical cohort of workers with occupational injury in a state-owned locomotive vehicles company in central China was followed up on the outcomes of RTW. Demographic, employment and medical information was retrieved from the company archival documents; and post-injury information was interviewed by structured questionnaires. Univariate analysis and Cox Regression Model were used to examine the associations between potential determinants and outcomes of RTW. RESULTS: Three hundred of the 323 cases (92.9%) eventually returned to work after the median absence of 43 days. Factors from socio-demographic, clinical, economic, and psychological domains affected RTW in the univariate analyses. The multivariate analysis indicated that age, injury severity, injury locus, injury nature, pain in the injury locus, self-report health status and pre-injury monthly salary were significant determinants of RTW. CONCLUSIONS: There were multidimensional factors affecting RTW after occupational injury. Proper clinical treatment and rehabilitation, as well as economic and social support to facilitate workers' RTW would be the priorities upon intervention. Future studies should be conducted in larger representative samples to confirm the findings and to develop a multidisciplinary intervention strategy towards promoting RTW.