Abstract Objective To investigate the usefulness of ¹⁸F-FDG PET-CT for assessing large-vessel (LV) involvement in patients with suspected giant cell arteritis (GCA) and a negative temporal artery biopsy (TAB). Methods A retrospective review of our hospital databases was conducted to identify patients with suspected GCA and negative TAB who underwent an ¹⁸F-FDG PET-CT in an attempt to confirm the diagnosis. The gold standard for GCA diagnosis was clinical confirmation after a follow-up period of at least 12 months. Results Out of the 127 patients included in the study, 73 were diagnosed with GCA after a detailed review of their medical records. Of the 73 patients finally diagnosed with GCA, ¹⁸F-FDG PET-CT was considered positive in 61 cases (83.5%). Among the 54 patients without GCA, ¹⁸F-FDG PET-CT was considered positive in only eight cases (14.8%), which included 1 case of Erdheim-Chester disease, 3 cases of IgG4-related disease, 1 case of sarcoidosis, and 3 cases of isolated aortitis. Overall, the diagnostic performance of ¹⁸F-FDG PET-CT for assessing LV involvement in patients finally diagnosed with GCA and negative TAB yielded a sensitivity of 83.5%, specificity of 85.1%, and a diagnostic accuracy of 84% with an area under the ROC curve of 0.844 (95% CI: 0.752 to 0.936). The sensitivity was 89% in occult systemic GCA and 100% in extracranial LV-GCA. Conclusion Our study confirms the utility of ¹⁸F-FDG PET-CT in patients presenting with suspected GCA and a negative TAB by demonstrating the presence of LV involvement across different subsets of the disease.