Background Increasing burn-out rates among gastroenterologists make it necessary to find ways to prevent burn-out and to stimulate their ability and willingness to continue working (i.e., their employability). Understanding their antecedents might help organizations to prevent burn-out and to enhance employability among this occupational group. Objective The purpose of this study is to provide insight in the relationship between job characteristics and job crafting behavior on the one hand and job outcomes (burn-out symptoms and employability) on the other hand. Methods Data from two surveys in 2020 and 2021 were collected in a longitudinal study among 238 Dutch gastroenterologists. The data were analyzed with multiple linear regression analyses and paired-samples t-tests. Results Job characteristics, specifically job aspects that require sustained physical and/or psychological effort or skills (i.e., job demands), are important predictors of burn-out symptoms among gastroenterologists. Specifically, high quantitative and emotional workload are significantly related to more burn-out symptoms. No strong relationship was found between job crafting and burn-out symptoms. Furthermore, job aspects that reduce the negative impact of these demanding aspects and that help to achieve work goals (i.e., job resources), and job demands to some extent, significantly predict employability. In particular, high job autonomy is related to higher employability, and high quantitative workload is associated with lower employability. Job crafting does not significantly affect employability. Furthermore, levels of burn-out symptoms and employability differed only little across time. Conclusion In gastroenterologists, a high quantitative workload and emotional workload are associated with a higher burn-out risk, while low job autonomy and high quantitative workload are associated with more negative perceptions of employability. To prevent burn-out and to create positive perceptions of employability, it is important to take these ...