OBJECTIVES: Congenital adrenal hyperplasia (CAH) comprises a group of disorders in which cortisol synthesis is disrupted. It may result in life-threatening adrenal crises and in symptoms such as genital ambiguity and hirsutism in females, precocious puberty, and infertility, with associated effects on well-being. The purpose of this study was to evaluate all-cause mortality and depression and to characterise clinical manifestations of CAH in a UK primary-care population. METHODS: Data were from the UK Clinical Practice Research Datalink (CPRD). Patients with a diagnosis of CAH and at least one prescription for a corticosteroid were selected, and matched 1:10 to a randomly drawn control group without CAH on gender, age and general practice. The mortality rate ratio was calculated and prevalence of depression compared. Additionally descriptive, non-comparative analysis of key clinical manifestations was presented. RESULTS: We identified 605 subjects with CAH (41% male). Mean age at presentation was 11.0 (sd 19.9) years for males, 13.6 (sd 17.4) for females. 58% of subjects were diagnosed ≤6 years old. 562 patients with CAH (93%) could each be matched with 10 controls. The crude rate ratio for all-cause mortality in CAH vs. controls was 2.6 (95%CI 1.7–3.9). Lifetime prevalence of depression in CAH was 33% vs. 26% in controls (p<0.001). In females the following morbidities were reported: adrenal crisis, hyponatraemia, 39 (11%); genital anomalies/surgery, 129 (36%); precocious puberty, 34 (10%); hirsutism, virilism, 65 (18%); polycystic ovarian syndrome, 36 (10%); oligo/amenorrhoea, 42 (12%); infertility, 37 (10%). In males the following were reported: adrenal crisis, hyponatraemia, 30 (12%); precocious puberty, 20 (8%); infertility, 12 (5%).  CONCLUSIONS: Patients with CAH had significantly reduced survival and increased prevalence of depression compared with matched controls. Novel approaches to treating CAH that can alleviate the impact of this condition are required urgently.