Glass ampoules provide stable medication storage, but their brittleness makes improper breaking techniques prone to uneven necks and sharp injuries. Up to 38% of nurses and nursing students report ampoule-related cuts, which may lead to bloodborne infection risk, psychological stress, financial burden, and medication contamination, affecting both healthcare workers and patients.To evaluate the effectiveness of an innovative ampoule-opening device in improving occupational safety during medication preparation.This randomized controlled trial enrolled clinical nurses from a medical center. Participants were assigned to one of three opening methods—alcohol swab + bare hand, scissors, or an ampoule-opening device—and instructed to break 5 mL, 10 mL, and 20 mL ampoules in randomized order. Data were analyzed using SPSS 25, and general linear regression was used to compare breaking time, sharp-injury occurrence, and neck defects across methods.A total of 108 nurses participated (86.1% female; mean age 28.63 ± 6.4 years). Only one sharp injury occurred in the alcohol swab + bare-hand group. The ampoule-opening device achieved the shortest breaking time for 5 mL and 10 mL ampoules and was faster than the bare-hand method for 20 mL ampoules (all P < .05). Compared with the device, scissors produced 0.86, 1.31, and 1.64 more neck defects for 5 mL, 10 mL, and 20 mL ampoules (all P < .05). The bare-hand method created slightly more defects (0.06, 0.42, 0.39), though differences were not statistically significant.Although not all outcomes reached statistical significance, the device reduced breaking time and generated smoother neck surfaces, while also lowering the risk of sharp injuries. The absence of cuts in other groups may reflect participants' increased caution and the controlled testing environment, which does not fully represent fast-paced clinical conditions. As an engineering control within the Hierarchy of Controls Framework, the device offers a practical strategy to enhance occupational safety and should be considered for use in clinical settings.Limited observed effects may reflect insufficient training with the ampoule-opening device. Future research should include adequate training, compare performance across healthcare roles, and assess cost-effectiveness to support broader clinical adoption. Keywords: accidental injuries, engineering controls, occupational safety, safety equipment