BACKGROUND: In many countries, a general shortage of nurses is a public health problem, and retention of nurses in active work is a challenge. The aim of this study was to ascertain whether the same individual factors, working conditions and health problems had led to increased probability of both leaving jobs and prolonged sickness absence in a cohort of Swedish nurses over a period of 3 years. METHODS: A baseline questionnaire was answered by 2293 nurses, representing a response rate of 86%. Exposed and unexposed nurses were compared with regard to two outcomes. During the 3-year follow-up, exposed and unexposed nurses were compared with regard to two outcomes: resigning and having at least one sick leave spell that lasted 28 days or longer. RESULTS: We found that 18% of the nurses left their employment, and 16% had sick leave spells > or =28 days. Work in geriatric care, being socially excluded by superiors and/or workmates, negative effects of organizational changes and poor self-rated general health were factors that increased the likelihood of both leaving jobs and long-term sick leave. CONCLUSIONS: The present results underline the importance of improving working conditions and supporting sustainable health in order to prevent high turnover and prolonged sick leave among nurses. Resigning and moving to another institution can be interpreted as a way to actively cope with an unhealthy work environment.