Background: Patients with adrenal insufficiency (AI) have excess mortality, in part due to the occurrence of life‐threatening adrenal crises. Infective processes, including that of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), are recognised as the major precipitant of adrenal crises. Adverse reactions to the ChAdOx1 SARS‐CoV‐2 vaccine occur in a significant proportion of individuals, however, are mild‐moderate in the majority of cases. Design: Case series. Patients & Results: We describe five cases where more severe adverse reactions to the ChAdOx1 SARS‐CoV‐2 vaccine led to actual or incipient adrenal crises requiring parenteral hydrocortisone within 24 h of receiving the first ChAdOx1 SARS‐CoV‐2 vaccination. Conclusion: In individuals with adrenal insufficiency, adverse reactions to the initial dose of the ChAdOx1 SARS‐CoV‐2 vaccination can precipitate adrenal crises. We recommend that patients with AI should immediately increase their maintenance glucocorticoid dosage 2–3 fold on experiencing any symptoms in the initial 24 h following vaccination. [ABSTRACT FROM AUTHOR]