OBJECTIVES: To quantify the resource utilization predictors and cost of cardiovascular disease using the Australian Reduction of Atherothrombosis for Continued Health (REACH) registry. METHODS: This paper describes two-year cost data estimated using a bottom-up costing approach, and presents patterns of resource utilization based on types of vascular disease. The multivariate predictors of number of hospitalization, medication and other health services used per patient and related costs at two-year follow-up were examined using generalized linear models (GLM). Government reimbursement data from 2011 was used to calculate direct health care costs.  RESULTS: Overall 2873 of the total 68 236 patients in the REACH registry cohort were enrolled from Australia. The two-year follow-up data was available for 2856 (99.4%) patients with or at high risk of atherothrombosis. Overall, the mean (SD) direct expenditure over 24 months of follow-up per person was $7544 ($10 758). In the adjusted model, patients with coronary artery disease (CAD) and peripheral arterial disease (PAD) incurred +A$1255 (95% CI $199 to $2310) and +A$4942 (95% CI $3509 to $6375) more in mean total costs compared to cerebrovascular (CerVD) patients respectively. A history of atrial fibrillation (AF), PAD and diabetes was associated with higher resource utilization. CONCLUSIONS: Our analysis has found that significant predictors of resource utilization and medical costs were PAD, AF, and diabetes. The results highlight the need for policies that target reducing the number of co-morbidities, which will decrease the incidence of PAD, AF and diabetes in population, given current and projected burden. This data provide the necessary framework for economic evaluations of health interventions.