Approximately 20% of healthcare workers in high-income countries such as Australia, Canada and the USA work in rural areas. Healthcare workers are known to be vulnerable to occupational injury and poor work disability outcomes; given their rural-urban distribution, it is possible to compare work disability prevention in rural and urban areas. However, little attention has been paid to work disability prevention issues specific to rural workers, including rural healthcare workers. A comprehensive review of the literature was conducted to identify rural-urban differences in work disability outcomes (defined as the incidence of occupational injury and the duration of associated work absence), as well as risk factors for poor work disability outcomes in rural healthcare workers. The databases MEDLINE, CINAHL, and EMBASE were searched, as were relevant research centers and government agencies, to identify all quantitative and qualitative English-language studies published between 1 January 2000 and 6 October 2009 that discussed occupational injury, work absence duration, work disability management, or risk factors for poor work disability outcomes, for rural workers specifically, or in comparison with urban workers. To ensure inclusion of studies of healthcare workers as a distinct group among other sector-specific groups, a broad search for literature related to all industrial sectors was conducted. Of 860 references identified, 5 discussed work disability outcomes and 25 discussed known risk factors. Known risk factors were defined as factors firmly established to be associated with poor work disability outcomes in the general worker population based on systematic reviews, well-established conceptual models of work disability prevention, and public health literature. Although somewhat conflicting, the evidence suggests that rural healthcare workers experience higher rates of occupational injury compared with urban healthcare workers, within occupational categories. Rural workers also appear to be more vulnerable to prolonged work absence although the data are limited. No studies directly compared risk factors for work disability prevention outcomes between rural and urban healthcare workers. However, potential risk factors were identified at the level of the environment, worker, job, organization, worker compensation system and healthcare access. Important methodological limitations were noted, including unclear definitions of rurality, inadequate methods of urban-rural comparisons such as comparing samples from different countries, and a paucity of studies applying longitudinal or multivariate designs. There is a notable lack of evidence about work disability prevention issues for healthcare workers in rural areas. Available evidence supports the hypothesis that rural healthcare workers are vulnerable to occupational injury, and suggests they are vulnerable to prolonged work absence. They may be particularly vulnerable to poor work disability prevention outcomes due to complex patient needs in the context of risk factors such as heavy workloads, long hours, heavy on-call demands, high stress levels, limited support and workplace violence. Additional vulnerability may occur because their work conditions are managed in distant urban administrative centers, and due to barriers in their own healthcare access. Although rural healthcare workers seem generally at greater risk of injury, one study suggests that urban emergency medical service workers experience a high vulnerability to injury that may outweigh the effects of rurality. Additional research is needed to document rural-urban disparities in work disability outcomes and to identify associated sources and risk factors. Other issues to address are access to and quality of healthcare for rural healthcare workers, streamlining the compensation system, the unique needs of Aboriginal healthcare workers, and the management of prolonged work absence. Finally, occupational injury and work absence duration programs should be tailored to meet the needs of rural workers.