Syncope and presyncope occurring during work can affect safety and impair occupational performance. Few data are available regarding the prevalence of these events among workers. The possible role of sleep quality, mental stress and metabolic disorders in promoting syncope, presyncope and falls in workers is unknown. In the present study, 741 workers (male 35.4%; mean age 47±11 years), employed in different companies, underwent clinical evaluation and blood tests and completed questionnaires to assess sleep quality, occupational distress and mental disorders. The occurrence of syncope, presyncope and unexplained falls during their working life was assessed by an ad hoc interview. The prevalence of syncope, presyncope and falls of unknown origin was 13.9%, 27.0%, and 10.3%, respectively. The occurrence of syncope was associated with an increased risk of occupational distress (adjusted Odds Ratio aOR: 1.62, Confidence Intervals at 95%: 1.05-2.52), low sleep quality (aOR: 1.79 CI 95%: 1.16-2.77) and poor mental health (aOR: 2.43 CI 95%: 1.52-3.87). Presyncope was strongly associated with occupational distress (aOR: 1.77 CI 95%: 1.25-2.49), low sleep quality (aOR: 2.95 CI 95%: 2.08-4.18) and poor mental health (aOR: 2.61 CI 95%: 1.78-3.84), while no significant relationship was found between syncope or presyncope and metabolic syndrome. These results suggest that occupational health promotion interventions aimed at improving sleep quality, reducing stressors and increasing worker resilience might reduce syncope and presyncope events in the working population.