Background: A disease-specific quality of life questionnaire is not available for patients with periampullary carcinoma, although cancer-specific questionnaires and the Gastrointestinal Quality of Life Index (GIQLI) have been used. The aim of this study was to validate the GIQLI for patients with periampullary tumours and to evaluate if subscales of the GIQLI could be identified to allow a more detailed assessment of the patients' quality of life. Methods: Patients with periampullary carcinoma, included in a study concerning diagnostic laparoscopy, were asked about symptoms and completed a questionnaire comprising the Medical Outcomes Study (MOS) 24 questionnaire, the GIQLI and one question of the Rotterdam Symptom Check List (RSCL). Clinical interpretation and statistical factor analysis were used to identify subscales of the GIQLI. Results: The GIQLI could be divided into four subscales, measuring physical well-being, mental well-being, digestion and defaecation. All four subscales had a good internal reliability and the construct validity was supported by the pattern of correlations with the MOS and RSCL as wed as differences in subscale scores for patients with or without certain symptoms. Conclusion: In patients with periampullary tumours the GIQLI can be divided into four subscales, measuring different aspects of quality of life. These subscales provide insight into the different problems affecting the patient.