Surgical Site Infection (SIS) is a common healthcare-associated infection that significantly impacts patient safety and financial losses for health systems. Enhancing nurses' knowledge and practice is an essential component in the prevention of the spread of infection. The study aims to assess the knowledge and practice of preventing surgical site infection among nurses. A cross-sectional study was conducted among 306 nurses in two public hospitals in Malaysia. Data were obtained from

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... stered questionnaires and analyzed using the IBM Statistical Packages for Social Science (SPSS) Window Version 23. This study revealed that 85.3 % of nurses had good knowledge, and 97.7 % had good practice regarding SSI prevention. However, there was no significant difference between the nurses' knowledge and practice towards Prevention SSI (x2: 1.10; p-value: 0.28). There was a statistically significant association between working unit/ward and the total knowledge score (x2:24.51; p-value: 0.01). Nurses who worked in the Operation Theatre were found to have higher percentage of good knowledge (n: 108; 35.3%). It can be concluded that the nurses had good knowledge and practice regarding surgical site infection. Successful strategies of infection control measures were the well-structured guidelines, continuing education programs, adequate supervision, good support, and regular basis of the necessary consumables and supplies.