Background Accurate clinical staging is crucial to managing gastrointestinal cancer, but fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT has limitations. Targeting fibroblast-activation protein is a newer diagnostic approach for the visualization of tumor stroma, and gallium 68 (68Ga)-labeled fibroblast-activation protein inhibitors (FAPIs), hereafter 68Ga-FAPIs, present a promising alternative to 18F-FDG. Purpose To compare the diagnostic efficacy of 68Ga-FAPI PET/CT in primary and metastatic lesions of gastrointestinal malignancies with that of 18F-FDG PET/CT. Materials and Methods Images from patients with gastric, duodenal, and colorectal cancers who underwent contemporaneous 18F-FDG and 68Ga-FAPI PET/CT between October 2019 through June 2020 were retrospectively analyzed. 18F-FDG and 68Ga-FAPI uptakes were compared by using the Wilcoxon signed-rank test. The McNemar test was used to compare the diagnostic performance between the two techniques. Results Thirty-five patients (median age, 64 years [interquartile range, 53-68 years]; 18 men) were evaluated. In treatment-naive patients (n = 19), 68Ga-FAPI PET/CT led to upstaging of the clinical TNM stage in four (21%) patients compared with 18F-FDG PET/CT. Tracer uptake was higher with 68Ga-FAPI PET/CT than with 18F-FDG PET/CT in primary lesions (gastric cancer: 12.7 vs 3.7, respectively, P = .003; colorectal cancer: 15.9 vs 7.9, P = .03), involved lymph nodes (6.7 vs 2.4, P < .001), and bone and visceral metastases (liver metastases: 9.7 vs 5.2, P < .001; peritoneal metastases: 8.4 vs 3.6, P < .001; bone metastases: 4.3 vs 2.2, P < .001; lung metastases: 4.4 vs 1.9, P = .01). In addition, the sensitivity of 68Ga-FAPI PET/CT was higher than that of 18F-FDG PET/CT in the detection of primary tumors (100% [19 of 19] vs 53% [10 of 19], respectively; P = .004), lymph nodes (79% [22 of 28] vs 54% [15 of 28], P < .001), and bone and visceral metastases (89% [31 of 35] vs 57% [20 of 35], P < .001). Conclusion Gallium 68 fibroblast-activation protein inhibitor PET/CT was superior to fluorine 18 fluorodeoxyglucose PET/CT in the detection of primary and metastatic lesions in gastric, duodenal, and colorectal cancers, with higher tracer uptake in most primary and metastatic lesions. Published under a CC BY 4.0 license.