COVID-19 vaccination may trigger reactive lymphadenopathy, confounding imaging interpretation. There has been limited systematic analysis of PET findings after COVID-19 vaccination. The purpose of this study was to evaluate the frequency and characteristics of abnormal FDG and C-choline uptake on PET performed after COVID-19 vaccination. This retrospective study included 67 patients (43 men and 24 women; mean [± SD] age, 75.6 ± 9.2 years) who underwent PET examination between December 14, 2020, and March 10, 2021, after COVID-19 vaccination and who had undergone prevaccination PET examination without visible axillary node uptake. A total of 52 patients received the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech; hereafter referred to as the Pfizer-BioNTech vaccine), and 15 received the SARS-CoV-2 mRNA-1273 vaccine (Moderna; hereafter referred to as the Moderna vaccine). Sixty-six of the patients underwent PET/CT, and one underwent PET/MRI. Fifty-four PET examinations used FDG, and 13 used C-choline. PET was performed a median of 13 and 10 days after vaccination for patients who had received one ( = 44) and two ( = 23) vaccine doses, respectively. Two nuclear medicine physicians independently reviewed images and were blinded to injection laterality and the number of days since vaccination. Lymph node or deltoid SUV greater than the blood pool SUV was considered positive. Interreader agreement was assessed, and the measurements made by the more experienced physician were used for subsequent analysis. Positive axillary lymph node uptake was observed in 10.4% (7/67) of patients (7.4% [4/54] of FDG examinations and 23.1% [3/13] of C-choline examinations); of the patients with positive axillary lymph nodes, four had received the Pfizer vaccine, and three had received the Moderna vaccine. Injection laterality was documented for five of seven patients with positive axillary lymph nodes and was ipsilateral to the positive node in all five patients. PET was performed within 24 days of vaccination for all patients with a positive node. One patient showed extraaxillary lymph node uptake (ipsilateral supraclavicular uptake on FDG PET). Ipsilateral deltoid uptake was present in 14.5% (8/55) of patients with documented injection laterality, including 42.9% (3/7) of patients with positive axillary lymph nodes. Interreader agreement for SUV measurements (expressed as intraclass correlation coefficients) ranged from 0.600 to 0.988. Increased axillary lymph node or ipsilateral deltoid uptake is occasionally observed on FDG or C-choline PET performed after COVID-19 vaccination with the Pfizer-BioNTech or Moderna vaccine. Interpreting physicians should recognize characteristics of abnormal uptake on PET after COVID-19 vaccination to guide optimal follow-up management and reduce unnecessary biopsies.