After the nuclear disaster in Fukushima on 11 March 2011, some businesses were permitted to continue operating even though they were located in the evacuation area designated by the Japanese government. The aim of this study was to examine differences in the mental health status, workplace, living environment, and lifestyle of employees in the evacuation and non-evacuation areas. We also investigated factors related to their mental health status. Data for this cross-sectional study were collected from the questionnaire responses of 647 employees at three medium-sized manufacturing companies in the evacuation and non-evacuation areas. Through a cross-tabulation analysis, employees who worked at companies in the evacuation areas showed an increase in the duration of overtime work, work burden, and commute time, and had experienced separation from family members due to the radiation disaster and perceived radiation risks. The results of a multivariate logistic regression analysis showed that, even in a harsh workplace and living environment, being younger, participating regularly in physical activity, having a social network (Lubben Social Network Scale-6 ≤ 12), laughing frequently, and feeling satisfied with one’s workplace and domestic life were significantly associated with maintaining a healthy mental health status after the disaster. These findings are applicable for workers’ health management measures after disasters.