OBJECTIVES: To estimate the cost-effectiveness of safety-engineered devices (SEDs) relative to non-SEDs for winged steel needles, intravenous (IV) catheter stylets, suture needles, and insulin pen needles. METHODS: We developed a decision-analytic model to estimate and compare the life-cycle costs and benefits for SED and non-SED needle devices. We utilized a hypothetical cohort of healthcare workers who utilized needle devices. For this cost-effectiveness analysis, we quantified the total direct medical cost per needlestick injury (NSI), number of NSIs avoided, and incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed to examine the robustness of the base-case analysis. RESULTS: In the base-case analysis, we calculated the ICERs of SED winged steel needles, IV catheter stylets, suture needles, and insulin pen needles to be $2,633, $13,943, $1,792, and $1,269 per NSI avoided, respectively. Sensitivity analyses showed that the calculated ICER values for using SEDs did not fall below zero even after adjusting the values of each parameter. CONCLUSIONS: The use of SED needle devices would not produce cost savings for hospitals. Government intervention may be needed to systematically protect healthcare workers in Japan from the risk of bloodborne pathogen infections.