Introduction: This study aims to define the role of flurodeoxyglucose ( 18F -FDG) positron emission tomography-contrast enhanced computed tomography (PETCECT) scan in upstaging disease in patients with locally advanced gallbladder cancer (LAGBC). Methods: An analysis of a prospectively maintained database of gallbladder cancer (GBC) patients was performed. Patients found to have locally advanced (T3 and/or T4 or N+) but non-metastatic disease on initial imaging, either a contrast enhanced computed tomography (CECT) or a magnetic resonance imaging (MRI) scan, underwent an additional PETCECT for staging and the results impacting treatment decision were recorded. Results: One hundred and three patients of LAGBC underwent CECT/MRI and PETCECT. 48/103 (46.6%) were found to be upstaged to stage IV after PETCECT.The most common metastatic site was non-regional retroperitoneal lymph nodes (12 patients, 11.7%) followed by satellite lesions in liver (11, 10.7%). Fourteen (13.6%) patients had equivocal findings on PET scan that required confirmation by tissue sampling out of which 10 (71.4%) were subsequently found to have metastatic disease. The only statistically significant factor predicting distant spread on PETCECT was the presence of loco-regional nodes on CT scan (odds ratio 6.15, P = .006). Conclusion: PETCECT is a valuable tool to rule out metastatic disease in patients presenting with LAGBC. K E Y W O R D S locally advanced gallbladder cancer, positron emission tomography-contrast enhanced computed tomography, staging How to cite this article: Patkar S, Chaturvedi A, Goel M, Rangarajan V, Sharma A, Engineer R. Role of positron emission tomography-contrast enhanced computed tomography in locally advanced gallbladder cancer. J Hepatobiliary Pancreat Sci. 2020;27:164-170. https ://doi.