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Background: Chronic spontaneous urticaria (CSU) is defined as the spontaneous occurrence of hives, angioedema, or both for more than 6 weeks; several inciting triggers including vaccines have been implicated. Coronavirus disease 2019 (COVID-19) vaccinations have been well tolerated by patients with CSU. However, reports have emerged of CSU triggered by COVID-19 vaccination and this study describes a South African case series. Objective: To provide details of the first case series of new-onset CSU post–COVID-19 vaccination in Africa and summarize the global literature of reported cases to date. Methods: All patients referred to our Urticaria Center of Excellence in Cape Town from the initiation of the COVID-19 vaccine rollout in South Africa (from February 2021 to August 2022) were reviewed to identify patients who developed new-onset CSU within 12 weeks of receiving a COVID-19 vaccine. Medical history, physical examinations, and laboratory investigations were reviewed. Results: More than 20 million adults received COVID-19 vaccinations in South Africa during the study period. Eight patients had new-onset chronic urticaria post–COVID-19 vaccination; 6 of the 8 patients were female, the median age was 41 years (interquartile range [IQR], 38-44), and all had a history of atopy. Only 1 reported COVID-19 infection post vaccination. Chronic urticaria occurred following Pfizer-BioNTech, AstraZeneca, and Janssen Ad26.COV2.S vaccination in 6, 1, and 1 patient, respectively, with a median of 12 days (IQR, 3-38) from vaccination to symptoms onset. The baseline median score for Urticarial Activity Score 7 was 34 (IQR, 29-40), and 5 of the 8 patients (63%) had a total IgE level of more than 43 IU/L. All patients received high-dose antihistamines, with only 3 patients controlled. Conclusions: New-onset CSU can rarely be triggered by COVID-19 vaccinations, most commonly mRNA vaccines. COVID-19 vaccine–triggered CSU appears to have a phenotype similar to that triggered by other inciting agents and across populations.