Needlestick and sharps injuries are the primary mechanism of occupational bloodborne pathogen transmission among healthcare workers. Approximately 385,000 sharps injuries occur annually in US hospitals. Hepatitis B virus (HBV) has the highest transmission risk per needlestick (6-30%), followed by hepatitis C virus (HCV) at 1.8%, and HIV at 0.3%. The Needlestick Safety and Prevention Act mandates use of engineered sharps injury prevention devices (safety needles, needleless IV systems). Hollow-bore needles carry higher transmission risk than solid sharps because they can contain larger volumes of blood. Post-exposure prophylaxis (PEP) must be initiated within hours of exposure: HBV immune globulin within 24 hours, HIV PEP ideally within 2 hours. Prevention strategies focus on engineering controls (safety devices), work practice controls (no recapping), and administrative controls (policies and training).