Context The European Organization for Research and Treatment of Cancer has developed the PAN26 instrument to measure quality of life in patients with pancreatic cancer. Its use has been increasing, but it has not yet undergone psychometric validation in a large cohort or in the setting of pancreatic resection. Objective We aimed to validate the PAN26 in patients undergoing pancreatic resection using a highquality Phase III clinical trial dataset. Methods The European Organization for Research and Treatment of Cancer core questionnaire and pancreatic cancer module were administered pre-operatively and at 14 and 60 days post-operatively to 300 patients enrolled in a Phase III trial of pasireotide to prevent pancreatic fistula. Multi-trait scaling analysis was performed; construct validity and internal consistency were assessed. Results With the exception of the hepatic scale, the PAN26 scales had adequate internal consistency (Cronbach’s alpha = 0.69 - 0.97), and items were more correlated with their own scale than other scales, indicating appropriate aggregation. Adenocarcinoma diagnosis was associated with worse scores on multiple scales. As expected, the PAN26 and C30 pain scales were highly correlated (>0.7). Conclusions In the largest psychometric analysis to date of the PAN26, we demonstrated that the scales are reliable and valid, although the appropriateness of the hepatic scale in the post-operative setting may need more examination. We observed differences by final diagnosis (adenocarcinoma or benign), and have shown previously that scores on symptom scales were worse post-operatively than at baseline, confirming the sensitivity of the PAN26 to detect clinically meaningful differences in quality of life. Received Jul