Purpose <p>Radiolabelled fibroblast activation protein inhibitors (FAPI) are promising molecular imaging tracers for the diagnosis and staging of pancreatobiliary cancer. To enable treatment response assessment with [⁶⁸Ga]Ga-FAPI-46, the day-to-day variability of its uptake must be defined. This study aimed to determine the repeatability of semi-quantitative [⁶⁸Ga]Ga-FAPI-46 PET/CT measurements in pancreatobiliary cancers.</p> Methods <p>Patients with pathologically confirmed pancreatobiliary cancer (pancreatic ductal adenocarcinoma (PDAC) or cholangiocarcinoma (CCA)) were included. Patients underwent two [⁶⁸Ga]Ga-FAPI-46 PET/CT scans, within 7 days, without any treatment before or between scans. Static long axial field-of-view (LAFOV) PET/CT scans were performed 60&#xa0;min post-injection of [⁶⁸Ga]Ga-FAPI-46 (EARL2-compliant reconstruction). Suspected malignant lesions were semi-automatically delineated (local background-adjusted 50% isocontour of the peak standardised uptake value (SUV)) and semi-quantitative measurements were extracted (SUV_mean, SUV_peak and SUV_max). Tumour-to-background ratios (TBR) were also calculated. Repeatability was assessed using the repeatability coefficient (RC) and the intraclass correlation coefficient (ICC).</p> Results <p>Twelve patients were included (seven PDAC, three perihilar CCA and two intrahepatic CCA). The median injected dose was 216 MBq (interquartile range (IQR) 167–266 MBq) and the median uptake time was 60&#xa0;min (range 60–68). In total, 70 FAPI-positive lesions were delineated. The RCs of SUV_mean, SUV_peak and SUV_max were 23.7%, 23.9% and 29.8%, respectively. For the blood pool adjusted TBR_mean, TBR_peak and TBR_max, the RC’s were 21.6%, 20.8% and 28.0%, respectively. All ICCs were above 0.98.</p> Conclusion <p>Semi-quantitative measurements of [⁶⁸Ga]Ga-FAPI-46 PET/CT have an excellent repeatability and can potentially be used in future studies to assess treatment response in pancreatobiliary cancers.</p>