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Introduction Nurses are exposed to significant risks from dangerous blood-borne pathogens (BBPs) through contaminated needles, sharp instruments, and splashes. The underreporting of needlestick and sharp injuries often prevents nurses from receiving post-exposure prophylaxis (PEP).Theory The study used the Health Belief Model (HBM) by Rosenstock, Hochbaum, and Kegels to understand health practices and behaviors.Method This cross-sectional study assessed the knowledge of PEP and adherence to needlestick injury (NSI) preventive measures among 300 nurses in hospitals in Udupi Taluk, Karnataka, using a self-administered questionnaire and an observational checklist.Results The participants had average knowledge (mean: 20.4 ± 3.20) and displayed fair adherence (35.3%) to NSI preventive measures (mean: 26.1 ± 3.42). Most nurses were aware of NSI reporting and first aid procedures, but only 38% understood the effectiveness of PEP against BBPs. Knowledge of PEP was associated with age (P = 0.001), work experience (P = 0.01), and previous NSI experiences (P = 0.006). Furthermore, adjusted regression analysis revealed that age (31–40 years), higher educational qualification (BSc and above), and area of work were significant predictors of adherence to NSI preventive measures, whereas gender and work experience were not independently associated with adherence.Discussion Although nurses had moderate knowledge of PEP, its application remained inconsistent. Key strategies, such as continuing education, performance audits, competency assessments, and hands-on training, are essential for enhancing nurses’ skills. Integrating these strategies into occupational safety policies may support improved adherence to NSI preventive measures and enhance the use of PEP among nurses.
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