OBJECTIVES: To implement methods for estimating direct medical costs from utilization data in the United Kingdom (UK). METHODS: We used 2006-2012 Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) inpatient hospital data to identify individuals with their first cardiovascular (CV)-related hospitalizations for myocardial infarction, ischemic stroke, heart failure, transient ischemic attack, unstable angina, and revascularization. We estimated the direct medical costs of hospitalizations, drugs, general practitioner (GP) visits, and referrals during the first 6-months (acute) and the subsequent 30-months (long-term) after the first CV event. Hospitalization costs were estimated using the 2013/2014 HRG Reference Costs Grouper software, processed with R (version 3.2.2). Drug costs were abstracted from NHS Drug Tariff lists and applied to anti-hypertensive, anti-thrombotic, anti-diabetic, and anti-hyperlipidemic drugs at the level of the drug and dose, multiplying the cost per dose unit by the quantity provided. GP visits were categorized as clinic, surgery, or telephone and costed using Personal Social Services Research Unit 2014 unit costs. Referrals were mapped to the closest specialist visit cost from NHS Reference Costs. Challenges included handling deprecated inpatient diagnosis codes, mapping text-based drug name fields between the cost and the prescription data, categorizing physician visits, and applying a hierarchy for CV event classification. RESULTS: We estimated costs for 24,093 patients. We costed 94,304 hospitalizations, 1,380,858 GP visits, 71,204 referral visits, and 2,571,243 prescription fills representing 855 unique drug and dose combinations. Mapping and categorization challenges were reconciled by a panel of clinicians. The mean acute period and mean annualized long-term period costs (2014 £) were £4060 and £1433 for hospitalizations, £436 and £619 for GP and referral visits, and £98 and £208 for drugs. CONCLUSIONS: Detailed costing using utilization data is feasible and representative of UK clinical practice, but is labor intensive. The economic burden of cardiovascular disease is substantial.