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Aim: Gastrointestinal (GI) symptoms are often reported by CF patients. Despite a proven relation to exocrine pancreatic insufficiency (PI), it remains unclear whether GI symptoms are related to the timing of pancreatic enzyme replacement therapy (PERT). Whereas most international recommendations suggest administration of PERT at the beginning of meals, it has not been studied whether such a proceeding is associated with lower burden of symptoms., Methods: Thirty CF patients aged 0-17 years of age with PI were randomised to four weeks of PERT prior to meals followed by four weeks of PERT after meals or vice versa. Using the CF-specific validated CFAbd-Score, abdominal pain, dysfunctional bowel habits and Quality of Life (QoL) related to GI symptoms were assessed in relation to the timing of PERT. Data were analysed using a linear mixed model., Results: There was no significant difference regarding abdominal pain, bowel habits or QoL related to GI symptoms when timing of PERT was changed from prior to after meals., Conclusion: No significant difference was found when administration mode of PERT changed from prior to after meals or vice versa. However, after an individual assessment, some patients may profit from changing administration mode of PERT from prior to after meals., (© 2021 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)