The objective of this study is to evaluate the incidence and cost of needlestick injuries (NIs) in the United States, United Kingdom, Germany, France, Italy, and Spain. Comprehensive search of peer-reviewed literature to gather information on the incidence and costs associated with NIs and a Web-based search to identify pertinent gray literature, trade associations, and key stakeholders for the prevention of NIs. The estimated annual incidence of NIs is 384,000 in the United States, 100,000 in the United Kingdom, 700,000 in Germany, 29,719 in France, 28,200 in Italy, and 21,815 in Spain. The economic burden of NIs varies from country to country; for instance, annual costs are estimated at €7 million in Italy and $118 million to $591 million in the United States. An accurate assessment of the incidence and economic burden of NIs is difficult to obtain because of widespread under-reporting. Furthermore, the projected costs do not account for long-term treatment costs resulting from possible infection with a blood-borne pathogen, absenteeism, worker’s compensation, or emotional repercussions. A significant proportion of NIs stem from injections and intravenous-related tasks, accounting for roughly one to two thirds of NIs in all countries examined. The US General Accounting Office estimates that 29% of NIs that occur in hospitals could be prevented through the adoption of safety-engineered needles or needle-free devices. In conclusion, findings on the incidence and economic burden of NIs indicate the need for safety-engineered needles or needle-free technology, along with increased education regarding safer practices in the work environment.