Aim To investigate how work‐related characteristics and work ability influence nursing staff decisions to change employer or leave the profession. Background Previous cross‐sectional studies have indicated that decreased work ability and unfavourable work‐related characteristics are important determinants for the intention to leave the profession among nursing staff. Methods A 1‐year longitudinal study, using data from the European Nurses' Early Exit Study. The study population consisted of 9927 (66%) members of the eligible nursing staff of which 345 left their current employer. Work‐related characteristics, work ability and employment status were assessed by questionnaires. Results Nursing staff with a low work ability were more likely to either change employer or leave the profession. Among nursing staff with a low work ability the risk of changing employer increased significantly with unfavourable work‐related characteristics. However, among nursing staff with a good work ability the risk of changing employer barely changed with unfavourable work‐related characteristics. Conclusion The negative effects of decreased work ability on changing employer and leaving the profession are partly counterbalanced by favourable psychological and physical work‐related characteristics. Implications for nursing management Managers should implement strategies that focus on promoting the work ability of nursing staff in combination with improving work‐related characteristics in order to prevent unnecessary changes of employment.