Background: While many scholars have acknowledged the relationship between personal and work-related factors associated with those looking for another job and actual turnover, there is a lack of longitudinal designs that test this relationship empirically. Objectives: This longitudinal study examines specific determinant factors that differentiate between so-called “stayers” and “leavers” within the nursing profession, and identifies risk factors for premature leaving by comparing nurses who have left their job, or the nursing profession, with nurses who stay. Methods: This cross-national exploratory European survey involved 34,587 nurses (baseline measurement) working in 623 hospitals, nursing homes, and home-based care organizations, and consisted of two measurements taken with a one-year time interval. The final samples for the follow-up measurement included 14,016 stayers and 866 leavers. As regards the leavers, the participating nurses were asked to indicate to what extent personal and work-related factors had contributed to their decision to leave their health care institution. Results: Nurses’ intent-to-leave scores were higher than the baseline measurement among those who left their organization during the twelve months that followed than they were among those who stayed (24.0% versus 13.5%). The majority of nurses (86.8%) who moved on left their profession voluntarily. Involuntary departure occurred more often in eastern European countries. Nurses indicated that their reasons for leaving were working conditions (e.g., relationship problems, emotional difficulties, time pressure and quality of care, dissatisfaction with use of one’s skills and lack of autonomy, work schedule difficulties, and dissatisfaction with pay) and family reasons (e.g. caring for relatives). For a considerable number of nurses, health reasons and the desire for further training added to their decision to leave. Discussion: Health care organizations should focus on implementing preventive measures in order to protect their labor market potential. Recommendations are made for human resource development in health care organizations and for further empirical research to better understand to what extent different policy systems across European countries explain the variance in outcomes.