The purpose of this study was to examine entrance examination-related stress, mental health, and the quality of life of high school students with and without irritable bowel syndrome. We administered a descriptive survey by collecting data from 1,877 students from eight schools in Gyeonggi province, Korea. This study employed the Rome III criteria for the assessment of irritable bowel syndrome, an entrance examination stress scale for measuring entrance examination-related stress, the revised Symptom Checklist-90-Revised for measuring mental health, and the World Health Organization Quality of Life Scale Abbreviated Version for measuring the quality of life. The frequency of irritable bowel syndrome in students was 19.0%. A majority had a mixed constipation and diarrhea subtype of irritable bowel syndrome. Compared with the high school students without irritable bowel syndrome, those with irritable bowel syndrome reported a significantly higher score on the entrance examination stress scale, Symptom Checklist-90-Revised, and World Health Organization Quality of Life Scale Abbreviated Version. Results suggest support for creating a high school education program that provides knowledge and information about irritable bowel syndrome to students. Furthermore, it is important to explore suitable therapeutic approaches and nursing interventions for this population.