Background: Blood transfusions are an important part of nursing procedure. Nurses play a key role in safely administering blood products to patients in surgical and critical care units. The aim of the study was to evaluate nurses' employment conditions as contributing factors affecting nurses' practice of safe blood transfusion in surgical and critical care units in Alexandria Main University Hospital. Subjects and Method: Study design: Descriptive analytical design; an observational research design. Setting: Surgical and critical care units in Alexandria Main University Hospital. Subjects:  The study was carried out on 350 nurses and 1000 processes of blood transfusions Study tools:  Data were collected using factors affecting safe blood transfusion questionnaire and nurses' practice of safe blood transfusion observational checklist. Results: The nurses' employment conditions affected the practice of safe blood transfusion among nurses in surgical and critical care units. A positive significant relationship and direct impact were found between nurses' practice and many factors as working in critical care units (OR= 1.29), professional  (OR=1.72), technical (OR=1.12), trained nurses (OR= 1.60), working experience  between 10 to 19 years (OR= 1.21) and more than 20 years (OR= 1.53), working 36 hours per week (OR=1.42)   and day  (OR= 1.66) and fixed shifts (OR=1.57).  Staff (r=-.682; OR=.92) and untrained nurses (OR=.25), working in surgical care units (OR=.84), working duration less than 10 years (OR=.81), long (OR=.23), night (OR=.16) and rotated shifts (OR=.68) and more than 36 hours per week (OR=.13) had negative relationships and indirect effect on the nurses' practice.   Two third of the studied nurses did not attain sufficient levels of practice of safe blood transfusion (66. 6 %).   Conclusion: Nurses' employment conditions were contributing factors affecting the practice of safe blood transfusion among nurses in surgical and critical care units. Recommendations: Establishing training programs related to safe blood transfusion, creating safety measures for blood transfusion practice and providing blood transfusion policies are essential strategies for enhancing nurses' practice of safe blood transfusion in surgical and critical care units.