Background: Code blue is generally used to indicate a patient requiring resuscitation or in need of immediate medical attention, most often as the result of a respiratory arrest or cardiac arrest. Every hospital as a part of its plans, sets a policy to determine which unit provides personnel or code blue coverage. It is very essential for every staff nurse to have an adequate knowledge regarding the code blue protocol to reduce the mortality rate especially in critical care units. A comparative study was conducted to assess the knowledge on code blue protocol between general ward and critical unit staff nurses at Mahatma Gandhi Medical College and Research Institute. Materials and methods: Descriptive research design was used to conduct this study. Sixty nurses (30 general ward nurses and 30 critical care unit nurses) selected by purposive sampling technique, from the general ward and critical care unit includes medical ward, surgical ward, orthopaedic ward and gynaecological ward at Mahatma Gandhi Medical College and Research Institute, Puducherry. The data collected by semi structured questionnaire to assess the knowledge on code blue protocol. Results: In critical care unit nurses, knowledge mean score is 19.30 and the standard deviation is 3.36. In general ward nurses, knowledge means the score is 15.23 and standard deviation is 2.19. The findings show that statistically highly significant (p ≤ 0.000). Conclusion:The critical care nurses are having more knowledge about code blue than general ward nurses. Code blue call is the life threatening scenario where it should be known to every nurse who was working in both critical care units and general wards.