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The prevention of needlestick injuries (NSIs) represents a challenge to safety and health of healthcare workers (HCWs) employed in Emergency Departments (EDs), globally. Although, by literature, the use of Safety Engineered Devices by HCWs represents an effective way to prevent NSIs, organisational interventions targeted to decrease job stress have been suggested effective in minimising the occurrence of NSIs. The purposes of the present multi-centre study were:to investigate the relationship between interventions focusing job stress and NSIs occurrence among nurses employed in Hospital EDs;to quantify the economic impact of such interventions on the safety budget.The authors compared the NSIs occurrence among nurses employed in three Hospital EDs in two 4 year periods, after and before organisational interventions aimed to manage job stress, respectively. Finally, the economic cost of NSIs occurrence was calculated. All analyses were performed using SPSS software for Windows.The cumulative 4 year incidence of NSIs occurred after organisational interventions focusing job stress was significantly lower than the cumulative 4 year incidence observed prior to such interventions (p<0,05). By results, significant cost saving from managing fewer NSIs than the previous period was found.In the present study, organisational interventions aimed at managing job stress revealed effective in preventing NSIs and, consequently, in decreasing the economic cost due to NSI occurrence. Furthermore, the authors demonstrated that a proactive, integrated and comprehensive management of job stress brings benefits to employees and reduces the burden of the NSIs occurrence. These findings highlight that the issues of job stress and workers’ safety are interconnected and hence, a special effort is required in order to minimise job stress with the aim to reach the goal of safe, health and productive workplaces in healthcare sector.