Objectives The aim of this study was to investigate the effect of ill health and socioeconomic status on labor force exit due to unemployment, early retirement, disability pension, or becoming economically inactive. A secondary objective was to investigate the effect of ill health and socioeconomic status on return to work. Methods A representative sample of the Dutch working population (N=15152) was selected for a prospective study with ten years follow-up (93917 person-years). Perceived health and individual and household characteristics were measured at baseline with the Permanent Quality of Life Survey (POLS) during 1999—2002. Statistics Netherlands ascertained employment status monthly from January 1999 to December 2008. Cox proportional hazards analyses were used to determine the factors that predicted labor force exit and return to work. Results Ill health increased the likelihood of labor force exit into unemployment [hazard ratio (HR) 1.89], disability pension (HR 6.39), and early retirement (HR 1.20), but was not a determinant of becoming economically inactive (HR 1.07). Workers with low socioeconomic status were, even after adjusting for ill health, more likely to leave the labor force due to unemployment, disability pension, and economic inactivity. Workers with ill health at baseline were less likely to return to work after unemployment (HR 0.75) or disability pension (HR 0.62). Socioeconomic status did not influence re-employment. Conclusions Ill health is an important determinant for entering and maintaining paid employment. Workers with lower education were at increased risk for health-based selection out of paid employment. Policies to improve labor force participation, especially among low socioeconomic level workers, should protect workers with health problems against exclusion from the labor force.