As employers respond to intensive global competition through the deregulation of labor, job insecurity has become a widespread problem. It has been shown to have significant health impacts in a growing number of workers, but less is known about its social distribution, the mechanisms through which it may act, and the moderating effects of gender, socioeconomic position, and company size. Utilizing data from a national survey of a representative sample of paid employees in Taiwan, we examined the prevalence of job insecurity and its associations with psychosocial work characteristics and health status. A total of 8705 men and 5986 women aged between 25 and 65 years old were studied. Information on perceived job insecurity, industrial and occupational types, psychosocial work characteristics as assessed by the Job Strain model, and various measures of health status were obtained by a self-administered questionnaire. The overall prevalence of job insecurity was high (50%). Job insecurity was more prevalent among employees with lower education attainment, in blue-collar and construction workers, those employed in smaller companies, and in older women. Insecure employees also reported lower job control, higher job demands, and poor workplace social support, as compared with those who held secure positions. Regression analyses showed that job insecurity was strongly associated with poor health, even with adjustment of age, job control, job demands, and work place social support. The deleterious effects of job insecurity appeared to be stronger in men than women, in women who held managerial or professional jobs than women in other employment grades, and in those working in larger companies than smaller ones. The findings of this study suggest that perceived job insecurity is an important source of stress, and it is accompanied with adverse psychosocial work conditions and poor health. High-risk groups were identified for further investigation.