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• 68Ga-FAPI PET/CT showed favourable tumour-to-background contrast compared to 18F-FDG PET/CT in oesophageal cancer. • SUV thresholds of FAPI ×20%, 30%, 40%, and FDG ×40% showed similar lesion lengths compared with endoscopic examination. • 68Ga-FAPI PET/CT may provide additional information for target volume delineation to avoid tumour geographic misses. To compare 68Ga-fibroblast activation protein inhibitor (FAPI) and 18F-FDG PET/CT in imaging locally advanced oesophageal cancer, and evaluate the potential usefulness of 68Ga-FAPI PET/CT on gross target volume (GTV) delineation aimed at radiotherapy planning for oesophageal cancer as compared with contrast-enhanced CT (CE-CT) and 18F-FDG PET/CT. Twenty-one patients with newly diagnosed oesophageal cancer who underwent both 18F-FDG and 68Ga-FAPI PET/CT scans were selected. GTVs of the primary tumours based on CE-CT (GTV CT), PET/CT, and CE-CT plus PET/CT were delineated. Gross tumour lengths were measured by GTVs and endoscopy and recorded. The 68Ga-FAPI PET showed significantly higher radiotracer uptake than 18F-FDG PET (median SUVmax 16.71 vs. 11.23; P = 0.002) in the primary tumours. SUV thresholds of FAPI ×20%, 30%, 40%, and FDG ×40% showed similar lesion lengths compared with that in endoscopic examination (P > 0.05). GTV CT demonstrated the largest volume (median: 48.80 mm3, range: 14.83–162.23 mm3) than PET-based GTVs. For PET/CT-guided complementary contouring of GTV CT , four patients (19%) were increased by FAPI ×20% and 30%, two patients (9.5%) were increased by FAPI ×40%, and only one patient was increased by FDG ×40%. Furthermore, the volume of GTV based on CE-CT plus FAPI ×20%, 30%, and 40% showed no significant difference with GTV CT and planning target volume based CE-CT plus FAPI-PET and meets the organ at risk standard. The 68Ga-FAPI PET/CT methodology showed favourable tumour-to-background contrast in oesophageal cancer and might provide additional information for target volume delineation and help avoid tumour geographic misses. [ABSTRACT FROM AUTHOR]