Abstract Aim Pancreaticoduodenectomy (PD) can severely impair quality of life (QOL) and alter normal activities. The European Organization for Research and Treatment of Cancer QOL questionnaire (EORTC QLQ-C30) is an integrated system for assessing QOL in cancer patients. The aim was to evaluate the QOL outcomes for patients who undergo PD over a six-month period peri-operatively. Method EORTC QLQ-C30 (v.3) and pancreas-specific (PAN26) questionnaires were offered to patients who underwent PD between July 2018 and March 2019. Patients were invited to complete the questionnaire three times (1–2 weeks pre-operatively, 2–6 weeks post discharge, and 6–8 months post-operatively. Patients were excluded if they did not complete >50% of the questions for at least two consecutive questionnaires. Scores were calculated in accordance with the EORTC QLQ-C30 (version 3) core questionnaire manual. Data was analysed using Cohen's effect size and one way analysis of variance (ANOVA). Results A total of 21 patients were included. Overall QOL was reduced post-discharge (mean score 70.4 (±23.6) vs. 54.6 (±21.0), d=1.628, p=0.0412), however, there was no difference between QOL scores pre-operatively and after 6 months. There was a significant difference after 6 months for physical (mean score 98.4 (±9.6) vs. 85.2 (±14.6), d=1.068, p=0.0017) and role (mean score 92.1 (±17.2) vs. 63.9 (±28.7), d=1.1919, p=0.0005) function-related questions. Reduced appetite, diet restriction and pain were worse following discharge but improved significantly after six months. Conclusions The results from this study suggest that whilst certain symptoms and functional impairment is common following PD, overall QOL returns to pre-operative levels for most patients.