Background Work-related aspects are important determinants of health for inflammatory bowel disease (IBD) patients. Aims We aimed to describe quality of working life (QWL) in IBD patients and to assess variables that are associated with QWL. Methods Employed IBD patients of two tertiary and two secondary referral hospitals were included. QWL (range 0-100) was measured using the Quality of Working Life Questionnaire (QWLQ). Work productivity (WP), fatigue, and health-related quality of life (HRQL) were assessed using the Work Productivity and Activity Impairment questionnaire, Multidimensional Fatigue Inventory, and Short Inflammatory Bowel Disease Questionnaire, respectively. Active disease was defined as a score > 4 for the patient-reported Harvey-Bradshaw index in Crohn's disease (CD) or Simple Clinical Colitis Activity Index in ulcerative colitis patients. Results In total, 510 IBD patients were included (59% female, 53% CD, mean age 43 (SD 12) years). The mean QWLQ score was 78 (SD 11). The lowest subscore (54 (SD 26)) was observed for "problems due to the health situation": 63% reported fatigue-related problems at work, 48% agreed being hampered at work, 46% had limited confidence in their body, and 48% felt insecure about the future due to their health situation. Intermediate/strong associations were found between QWL and fatigue (r = − 0.543, p < 0.001), HRQL (r = 0.527, p < 0.001), WP loss (r = − 0.453, p < 0.001) and disease activity (r = − 0.331, p < 0.001). Independent predictors of impaired QWL in hierarchical regression analyses were fatigue (B = − 0.204, p < 0.001), WP loss (B = − 0.070, p < 0.001), and impaired HRQL (B = 0.248, p = 0.001). Conclusions IBD-related problems at work negatively influence QWL. Fatigue, reduced HRQL, and WP loss were independent predictors of impaired QWL in IBD.