Sharp injuries, determining the risk of bloodborne infections and psychological distress in healthcare workers, may be prevented by a set of strategies, legally enforced in Europe through the Directive 2010/32/EU. To assess its level of implementation in Italy, a national survey was conducted in 2017 and again in 2021, evaluating the progress and possible drawbacks of the COVID-19 pandemic. Altogether, 285 safety managers and 330 nurses from a representative sample of 97 and 117 public hospitals were interviewed using a standardized questionnaire. Knowledge of the Directive requirements decreased significantly, with <60% of participants answering correctly in 2021, and nurses’ attendance in specific courses dropped to 25% in 2021 compared to 54% in 2017. Over 75% of hospitals introduced multiple safety-engineered devices (SED), though total replacement occurred in <50% of cases; routine SED availability increased for blood collection (89%) and venous access devices (83%). Incorrect behaviors in handling sharps decreased significantly over time. Nurses’ HBV vaccination coverage was high (89% in both surveys); in the last year, 97% were vaccinated against COVID, and 47% against influenza. Average annual injuries per hospital did not increase significantly (32 in 2021 vs. 26 in 2017). In 2017, nurses’ perceived safety barriers were working in emergency situations (49%) and lack of resources (40%); in 2021, understaffing (73%), physical fatigue (62%), and handling difficulties while wearing full protective equipment (59%). Safety measures were implemented in Italian hospitals, and although the average injuries per hospital did not show a decrease, these measures could have helped protect healthcare workers during the pandemic, mitigating its potential impact on the increase in situations at risk of injury.