Abstract Background Cardiac amyloidosis (CA) is associated with a high mortality rate due to sudden or progressive heart failure. It is often misdiagnosed due to non-specific symptoms, and its true incidence and prevalence in the United Kingdom (UK) remain uncertain. Purpose To describe patient characteristics and incidence of CA in the UK clinical setting using electronic health records. Methods In this retrospective observational study, anonymised, linked primary and secondary care data (Clinical Practice Research Datalink, CPRD and Hospital Episode Statistics, HES) were used to describe individuals diagnosed with CA. The CPRD database contains de-identified patient data sourced from a sample of general practitioner (GP) practices in the UK. Patients aged 18 years and older with a recorded Read or SNOMED-CT diagnosis code for CA or record of treatment with tafamidis (a licensed but not reimbursed treatment for transthyretin amyloid cardiomyopathy, ATTR-CM in the UK) in the period between January 2004 to December 2021 were included. The index date was defined as the earliest recorded date of CA diagnosis or tafamidis treatment. Demographic and clinical data were summarised using descriptive statistics. Incidence rates were reported per 100,000 person-years (PY). Results There were a total of 3,788 patients with CA (mean age: 67 years; 61% males) of which only 277 were coded as having wild-type transthyretin (ATTRwt) CA in mostly older patients (mean age: 79 years). The low patient counts of ATTRwt amyloidosis could be attributed to the lack of specificity in CA types and the low utilisation of ATTR amyloidosis codes. Heart Failure, essential hypertension and dyspnoea were the most common clinical presentations recorded in the 12 months to first diagnosis code or tafamidis prescription for CA (Table). The incidence of CA varied from 0.75 in 2004 to a peak of 1.96 in 2021, per 100,000 PY; a 2.9-fold increase in newly coded diagnoses in CA. There was a slight decline in the rates in 2020 and 2021 (Figure). Incidence rates in males and females increased over the 17-year period, with males consistently having higher rates than females. The incidence rate in females started from a lower base at 0.62/100,000 PY in 2004, increased by a factor of 1.9 to 1.1/100,000 PY, whereas in males it started at 0.88/100,000 PY and rose by a factor of 2.9 to 2.5 /100,000 PY. Incidence rates in subgroup populations have also been analysed. Conclusions In the UK clinical setting, the incidence rate of newly coded CA increased overall between 2004 and 2021, as well as in both male and female subgroups. The data suggest CA is becoming more common, or that awareness has improved, and there is now an urgent need for enhanced methods of detection, characterisation, and the need for thorough data capture to shape future pathway advancements.