Context: Surgical Site Infections (SSIs) are devastating conditions that affect the patients’ lives and health. Limitation of SSIs risks is guided by the preventive measures taken by practitioners of surgical wound care in surgical procedures. Aims: Evaluating knowledge and practice of healthcare professionals towards prevention of surgical site infection, and measuring the incidence of SSI. Settings and Design: A cross-sectional descriptive study conducted in Buraidah city. Included 218 healthcare professionals, from 2 public hospitals, were providing care to the surgical patients. However, those who were not dealing with the surgical care were excluded from the study. Methods and Material: Data attained on a prior used validated questionnaire. Statistical analysis used: Data were analyzed by using t-test, Chi-squared test and one-way ANOVA at P<0.05 level. Results: Knowledge regarding SSI prevention was insufficient with only 25.4% and 18.3% knowledgeable King Fahad Specialist Hospital (KFSH) and Buraidah Central Hospital (BCH) participants (mean score 16.01, 14.30 respectively). While the practice level was of a good level with 93.8% and 89.3% of KFSH and BCH participants respectively (mean score 33.72, 32.23). SSI incidence during year of 2017 was underreported with only 0.46% in KFSH and 0.05% in last 6months of the year in BCH. Conclusions: Knowledge and practice towards prevention of surgical site infection among KFSH and BCH healthcare professionals were measured. Level of knowledge found to be insufficient in both settings. While practice level was observed to be very good in both settings. SSI incidence rate during year of 2017 was underreported in general.