Background F-18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is a promising tool for diagnosing relapsing polychondritis (RP). However, its usefulness in assessing RP with airway involvement is unknown. Objective This study aimed to further evaluate and confirm the potency of F-18-FDG PET/CT in diagnosing RP with airway involvement and monitoring response to steroid-based therapy. Methods A total of 30 patients from a dedicated respiratory centre, diagnosed with RP in accordance with McAdam, Damiani or Levine criteria, were included in this study. All patients underwent baseline F-18-FDG PET/CT, and 10 patients underwent second scans after 2.5-15 months of steroid-based therapy. Visual scores (VS) and maximal standard uptake values (SUVmax) were analysed. Results In the initial scan, 83.3% (25/30) of patients were found to have FDG uptake in more than one cartilage. The median VS and SUVmax in the cartilages were 3 (range, 1-3) and 3.8 (range, 1.9-17.9), respectively. Positive rates for PET/CT-guided biopsy in nasal, auricular, and tracheal/bronchial cartilages were 100% (5/5), 88.9% (8/9), and 10.5% (2/19), respectively, but the positive biopsy rate in the auricular cartilage was 92.3% (12/13) even without PET/CT assessment. Based on biopsy-proven sites, the sensitivity of PET/CT was 55.6%, and the specificity was 5.3%. Compared with the baseline scan, the second scan showed much lower median VS (2 vs 3, respectively; p < 0.0001) and SUVmax (2.9 vs 3.8, respectively; p < 0.001). Of 10 patients who underwent second PET/CT, 8 had complete therapeutic response, while 2 had partial response. Conclusion F-18-FDG PET/CT assists in identifying multiple cartilage involvement in RP, but it seems neither a sensitive nor specific modality in diagnosing RP with airway involvement. Moreover, PET/CT has limited utility in locating biopsy sites and monitoring therapeutic response to corticosteroids.