Background: Blood transfusion is the transfusing of a compatible donor’s whole blood or any of its components to the recipient to correct/ treat any related clinical condition. The transfusion of blood products is essential for restoring the body’s oxygen transport capacity, or replenishing lost or depleted blood components in various medical conditions. Objectives: To assess knowledge and practice score regarding blood transfusion among staff nurses and to identify the association of knowledge score and practice score with selected demographic variables. Methodology: A descriptive research design that involved convenience sampling technique to collect data from the 60 staff nurses working at Sher-i-Kashmir Institute of Medical Sciences, Kashmir, using a “self-structured knowledge questionnaire and practice checklist”. Results: The study revealed that most of the staff nurses, i.e. 53.3%, had fair knowledge, 41.7% had poor knowledge, and only 5% of staff nurses had good knowledge regarding blood transfusion. The mean ± SD knowledge score of the staff nurses was 23.516 ± 4.59. Most of the staff nurses, i.e. 66.7%, had satisfactory practice, and 33.3% had unsatisfactory practice. The mean ± SD practice score of staff nurses regarding blood transfusion was 49.26 ± 6.40. A statistically significant association was found between nurses’ knowledge and demographic variables viz., age, professional qualification, clinical experience, the approximate number of blood transfusions performed in past 6 months, and in-service training programme attended regarding blood transfusion, and practice with demographic variables, viz., gender and clinical experience at p ≤ 0.05. Conclusion: The study concluded that deficiency of knowledge among nurses regarding blood transfusion threatens patients’ safety, and may also put patients in life-threatening conditions.