Purpose: Simulation-based education combined with mastery learning is more effective than simulation-based education alone. This study aimed to evaluate its effectiveness with regard to both technical and non-technical skills of simulation-based mastery learning (SBML) in blood transfusion training among undergraduate nursing students. Method: A nonequivalent control group pretest-posttest design was used. Fifty-one second-year students at a college of nursing in W city, South Korea, who had not started clinical practice were selected by convenience sampling and allocated to either the experimental or control group using the zigzag method. SBML program was consisted of a diagnostic test, repeated learning and formative assessments for non-passers. All outcome variables were measured before and after completion of the program. Results: The experimental group showed significantly increased performance scores of blood transfusion as compared to the control group (z=29.50, p<.001), with better outcomes in number of students achieving minimum passing score (χ2 =20.07, p<.001), self-confidence (F=17.68, p<.001), and communication skills (z=166.00, p=.003). Conclusion: This program was effective for undergraduate students to better improvement in performance, self-confidence, and communication skills, which can ensure greater safety in the transfusion. The results suggest that SBML ensures skill acquisition for clinical practice through improved performances in both technical and non-technical skills.