The occurrence and course of immune-mediated diseases (IMDs) following COVID-19 vaccination has been little explored so far. We retrieved, among adult patients hospitalized at the Internal Department of a French university hospital up to May 2022, all those who had developed, or relapsed to, an IMD less than 3 weeks following COVID-19 vaccination, without other triggers. Twenty-seven (24 new-onset) post-COVID-19 vaccine IMDs were recorded. They comprised giant cell arteritis or polymyalgia rheumatica ( = 16, HLA-DRB1*04 in 58% of 12 assessed GCA cases), immune-mediated necrotizing myositis or acute rhabdomyolysis, systemic vasculitis, immune thrombocytopenic purpura, rheumatoid arthritis, anti-synthetase syndrome, and adult-onset Still's disease. The causative vaccines were mRNA-based (20 cases) or viral vector-based (7 cases). The IMD typically occurred after the first vaccine dose, with an average delay of 8 (5 SD) days. The patients' mean age was 67 years, and 58% were women. The IMDs had protracted courses in all but three of the patients and typically required high-dose glucocorticoids, in combination with immunomodulators in 13 patients. One patient died of intractable rhabdomyolysis, whereas five suffered permanent damage from IMDs. Eleven patients with well-controlled IMDs completed their COVID-19 vaccination schedule, and two suffered mild IMD relapses. There is a risk of IMDs, notably GCA/PMR, and muscle disorders, following COVID-19 vaccination. Such adverse reactions typically occurred after the first dose, raising concern about subsequent COVID-19 vaccinations. However, early re-challenge in well-controlled IMDs appeared safe.