Objectives: To-date, several studies have evaluated the cost-effectiveness of coronary artery bypass grafting surgery (CABG) surgery versus percutaneous coronary intervention (PCI) using data from randomised controlled trials. This study will investigate the real-world cost-effectiveness of CABG compared with PCI with stents in high-risk patients with multi-vessel coronary artery disease (MVCAD). An Australian public hospital payer perspective will be adopted. Methods: Data for 3508 patients (CABG: N=1,440; PCI:N=2,068 ) admitted to a major metropolitan hospital was obtained from two clinical registries, the Melbourne Interventional Group (MIG) and the Australian & New Zealand Society of Cardiac & Thoracic Surgeons (ANZSCTS). Hospital readmissions and related patient-level costs were obtained for the period of June 2009 to December 2014, from the same institution. The maximum follow-up period was five years. Adjustments for inflation and discounting will be performed over this period. Propensity score matching through the Nearest Neighbour technique will be used to balance the characteristics between the treatment (CABG) and comparator (PCI) groups. The primary and secondary measures of effectiveness will be major adverse cerebrovascular and cardiac events (MACCE), and mortality, respectively. The incremental cost-effectiveness ratios (ICERs) per MACCE avoided, and life years gained will be evaluated. Propensity score bin bootstrapping (PSBB) will be performed to further validate the results. Results: Although several limitations apply to this analysis, we expect results to be similar to existing literature, which favours CABG compared with PCI with stents in the medium to long term. We expect highly favourable ICERs for CABG in sub-groups of patients at highest risk of complications. Conclusions: This study will reveal the costeffectiveness of CABG compared with PCI using real-world data and new propensity score techniques.