Twenty core nursing skills have been identified by the Korean Accreditation Board of Nursing Education. Proficiency in these skills is essential for all nursing professions, and many educational strategies exist to develop these skills in nursing students, including the Objective Structured Clinical Examination (OSCE). To date, no study on the effects of the OSCE on nursing education has been published. Therefore, we evaluated the effects of the OSCE on the core nursing skills of 207 pre-licensure nursing students in Korea. We measured the nursing students’ confidence, skills, and knowledge acquisition and retention. A one-way analysis of variance and Fisher’s least significant difference were used for data analysis. Among the four nursing areas (fall, transfusion, pre-operative, and post-operative), students demonstrated the highest confidence level scores in pre-operative nursing. On the OSCE, students scored the highest in transfusion nursing. Significant differences were found between prior knowledge, knowledge acquisition, and retention. Our findings confirm that the OSCE, after lectures and core nursing skill practice, improved the retention of nursing students’ knowledge. Therefore, this program can positively influence nursing students’ knowledge level, and implementing the OSCE can strengthen students’ clinical competency.