Inflammatory bowel disease (IBD) affects health-related quality of life (HRQoL). The Short Inflammatory Bowel Disease Questionnaire (SIBDQ) score is strongly correlated with HRQoL in IBD patients. This study aimed to assess the factors influencing HRQoL in IBD patients. In this prospective study, all patients with ulcerative colitis (UC) and Crohn's disease (CD) completed the SIBDQ at enrollment; some patients also completed a second SIBDQ at follow-up. Multiple linear regression analysis was used to determine associations between SIBDQ scores and clinical factors. A total of 1,020 patients participated (UC, 67%; CD, 33%). The median SIBDQ score was 52 (interquartile range, 44 to 59). In UC patients, the stool frequency (β=-2.333, p<0.001), Physician Global Assessment score (β=-3.950, p<0.001), fecal calprotectin level (β=-4.014, p<0.001), and corticosteroid use (β=-4.809, p=0.006) were negatively correlated with the SIBDQ score. In CD patients, the number of diarrhea episodes per day (β=-1.467, p=0.024) and Crohn's Disease Activity Index score (β=-0.045, p<0.001) were negatively correlated with the SIBDQ score. A total of 202 patients completed the second SIBDQ within a mean of 3.4 years. The distributions of SIBDQ score changes were as follows: decrease >10%, 28%; -10%10%, 43%. In both the initial SIBDQ and follow-up SIBDQ, scores for items pertaining to systemic symptoms (tension and fatigue) were relatively low. Bowel movement-related problems significantly affect the HRQoL of both UC and CD patients. IBD patients scored lower on SIBDQ items related to general well-being. After 3 years of follow-up at the IBD clinic, 43% of patients showed a significant improvement in HRQoL.