Simple SummaryPost-anti-COVID-19 vaccine lymphadenopathy is a not uncommon event. In this study, we investigated the multiparametric ultrasound findings of patients with post-vaccine lymphadenopathy and compared these findings among different anti-COVID-19 vaccines. We evaluated patients presenting with post-anti-COVID-19 lymphadenopathy. The presence, size, location, number, morphology, cortex–hilum, superb microvascular imaging and elastosonography of lymph nodes were assessed. They were axillary and supraclavicular ipsilateral to the injection site. Prevalent ultrasound features included oval morphology, asymmetric cortex with hilum evidence, central and peripheral vascular signals at superb microvascular imaging and elastosonography patterns similar to the surrounding tissue. We found no significant differences between the three COVID-19 vaccines: the Pfizer/BioNTech BNT162b2 mRNA vaccine, the AstraZeneca ChAdOx1 vaccine and Moderna’s mRNA-1273 vaccine. Some ultrasound lymph node features, such as round morphology, no hilum evidence and hard pattern, may mimic pathological lymph nodes. An awareness of the patient’s history (vaccine injection and oncological history) and ultrasound findings may help in the early recognition of this clinical scenario and in the appropriate selection of patients for a short-term US follow-up.Background: Post-anti-COVID-19 vaccine lymphadenopathy has recently been described in the literature. In this study, we investigated the multiparametric US findings of patients with post-vaccine lymphadenopathy and compared these findings among different anti-COVID-19 vaccines. Methods: We retrospectively evaluated 24 patients who underwent US between January and May 2021 due to post-anti-COVID-19 lymphadenopathy. The presence, size, location, number, morphology, cortex-hilum, superb microvascular imaging (SMI) and elastosonography of lymph nodes were assessed. Descriptive statistics were calculated and differences among anti-COVID-19 vaccines were analyzed using the Kruskal–Wallis test. A p-value ≤ 0.05 was considered statistically significant. Results: Sixty-six nodes were assessed. They were axillary (mean 1.6 cm ± 0.16) in 11 patients (45.8%) and supraclavicular (mean 0.9 cm ± 0.19) in 13 patients (54.2%). In 20 patients (83.3%), the number of nodes was ≤3. Prevalent US features included oval morphology (18, 75%), asymmetric cortex with hilum evidence (9, 37.5%), central and peripheral vascular signals (12, 50%) at SMI and elastosonography patterns similar to the surrounding tissue (15, 71.4%). No significant differences among the three anti-COVID-19 vaccines were observed (p > 0.05). Conclusions: Anti-COVID-19 vaccines may present lymphadenopathy with “worrisome” US features regarding size, shape, morphology, cortex-hilum, SMI and elastosonography. An awareness of the patient’s history and US findings may help in the early recognition of this clinical scenario and in the appropriate selection of patients for a short-term US follow-up.