ObjectivesWe aimed to investigate the role of [68Ga]FAPI-04 and [18F]FDG dual-tracer PET/CT for the initial assessment of gastric cancer and to explore the factors associated with their uptake.MethodsThis study enrolled 62 patients with histopathologically confirmed gastric cancer. We compared the diagnostic performance of [68Ga]FAPI-04, [18F]FDG, and combined dual-tracer PET/CT. The standardized uptake value (SUV) and tumor-to-background ratio (TBR) were also measured, and the factors that influence tracer uptake were analyzed.Results[68Ga]FAPI-04 PET/CT detected more primary lesions (90.3% vs 77.4%,p= 0.008) and peritoneal metastases (91.7% vs 41.7%,p= 0.031) and demonstrated higher SUVmaxand TBR values (p< 0.001) of primary lesions compared to [18F]FDG PET/CT. Dual-tracer PET/CT significantly improved the diagnostic sensitivity for the detection of distant metastases, compared with stand-alone [18F]FDG (97.1% vs 73.5%,p= 0.008) or [68Ga]FAPI-04 (97.1% vs 76.5%,p= 0.016) PET/CT. Subsequently, treatment strategies were changed in nine patients following [68Ga]FAPI-04 and [18F]FDG dual-tracer PET/CT. Nevertheless, [68Ga]FAPI-04 uptake was primarily influenced by the size and invasion depth of the tumor. Both [68Ga]FAPI-04 and [18F]FDG PET/CT showed limited sensitivity for detecting early gastric cancer (EGC) (37.5% vs 25.0%,p> 0.05).ConclusionsIn this initial study, [68Ga]FAPI-04 and [18F]FDG dual-tracer PET/CT were complementary and improved sensitivity for the detection of distant metastases pre-treatment in gastric cancer and could improve treatment stratification in the future. [68Ga]FAPI-04 had limited efficacy in detecting EGC.Key Points•[68Ga]FAPI-04 and[18F]FDG dual-tracer PET/CT are complementary to each other for improving diagnostic sensitivity in the initial evaluation of distant metastases from gastric cancer.•[68Ga]FAPI-04 PET/CT showed limited sensitivity in detecting EGC.• Need for further validation in a larger multi-centre prospective study.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00330-022-09321-1.