Abstract Background Work-related stress is widely recognized as one of the major challenges to occupational health and safety. The correlation between work-related stress risk factors and physical health outcomes is widely acknowledged. This study investigated socio-demographic and occupational variables involved in perceived risk of work-related stress. Methods The Italian version of the Health and Safety Executive Management Standards Indicator Tool was used in a large survey to examine the relationship between work-related stress risks and workers’ demographic and occupational characteristics. Out of 8,527 questionnaires distributed among workers (from 75 organizations) 6,378 were returned compiled (74.8%); a set of mixed effects models were adopted to test single and combined effects of the variables on work-related stress risk. Results Female workers reported lower scores on control and peer support and more negative perceptions of relationships and change at work than male workers, most of them with full-time contracts. Age, job seniority, and educational level appeared positively correlated with control at work, but negatively with job demands. Fixed-term workers had positive perceptions regarding job demands and relationships, but more difficulties about their role at work than permanent workers. A commuting time longer than one hour and shift work appeared to be associated with higher levels of risk factors for work-related stress (except for role), the latter having more negative effects, increasing with age. Conclusions The findings suggest that the assessment and management of work-related stress risk should consider specific socio-demographic and occupational risk factors such as gender, age, educational level, job status, shift work, commuting time, job contracts.