Abstract Context Mortality and infection-related hospital admissions are increased in patients with primary adrenal insufficiency (PAI). However, the risk of primary care–managed infections in patients with PAI is unknown. Objective To estimate infection risk in PAI due to Addison’s disease (AD) and congenital adrenal hyperplasia (CAH) in a primary care setting. Design Retrospective cohort study using UK data collected from 1995 to 2018. Main outcome measures Incidence of lower respiratory tract infections (LRTIs), urinary tract infections (UTIs), gastrointestinal infections (GIIs), and prescription counts of antimicrobials in adult PAI patients compared to unexposed controls. Results A diagnosis of PAI was established in 1580 AD patients (mean age 51.7 years) and 602 CAH patients (mean age 35.4 years). All AD patients and 42% of CAH patients were prescribed glucocorticoids, most frequently hydrocortisone in AD (82%) and prednisolone in CAH (50%). AD and CAH patients exposed to glucocorticoids, but not CAH patients without glucocorticoid treatment, had a significantly increased risk of LRTIs (adjusted incidence rate ratio AD 2.11 [95% confidence interval (CI) 1.64–2.69], CAH 3.23 [95% CI 1.21–8.61]), UTIs (AD 1.51 [95% CI 1.29–1.77], CAH 2.20 [95% CI 1.43–3.34]), and GIIs (AD 3.80 [95% CI 2.99–4.84], CAH 1.93 [95% CI 1.06–3.52]). This was mirrored by increased prescription of antibiotics (AD 1.73 [95% CI 1.69–1.77], CAH 1.77 [95% CI 1.66–1.89]) and antifungals (AD 1.89 [95% CI 1.74–2.05], CAH 1.91 [95% CI 1.50–2.43]). Conclusions There is an increased risk of infections and antimicrobial use in PAI in the primary care setting at least partially linked to glucocorticoid treatment. Future studies will need to address whether more physiological glucocorticoid replacement modes could reduce this risk.