OBJECTIVES: The IMS CORE Diabetes Model (CDM) is a widely published and validated decision support tool. The model uses UKPDS68 and UKPDS82 risk equations (REs) to predict events and has been updated to include REs from the Swedish-National-Diabetes-Registry (S-NDR) and the ADVANCE-Risk-Engine (A-RE). The objective of this study was to compare and contrast cardiovascular (CV) incidence and cost-effectiveness (CE) across these four REs. METHODS: Lifetime analyses comparing the CE of metformin+ sulphonylurea (M+S) versus metformin + DPP-4 (M+D) was undertaken using the CDM. Basal insulin rescue therapy (BI) was applied to both arms at HbA1c threshold levels of 7.5%. Efficacy data for dual therapy was sourced from a published mixed treatment comparison; HbA1c and BMI change at one-year of -0.8% and 0.199kg/m2 (M+D);-0.79% and 0.707kg/m2 (M+S) and -0.82 and 0.545 kg/m2 (BI), respectively, were applied. Hypoglycemia rates were taken from the same systematic review. US 2012 costs were used and discounting was applied at 3.0%. RESULTS: In the base analysis (UKPDS68) predicted CV incidence for myocardial infarction, stroke, ischemic heart disease and heart failure was 31.42%, 15.59%, 12.85% and 21.01%, respectively, for patients treated with M+D and 31.39% , 15.23%, 12.51% and 21.26% for patients treated with M+S. This compared to 26.72%, 14.31%, 17.96% and 12.74% (M+D) and 26.02%, 13.94%, 17.91% and 13.43% (M+S) using UKPDS82 REs; 30.19%, 52.93%, 6.42% and 6.22% (M+D) and 29.7%, 53.98%, 6.23% and 6.5% (M+S) using S-NDR REs and 42.62%, 15.05%, 11.98% and 19.56% (M+D) and 42.17%, 15.1%, 11.97% and 20.46% (M+S) using A-RE REs. Incremental cost per quality adjusted life years were estimated at $78,537 (UKPDS68); $77,594 (UKPDS82); $70,054 (S-NDR) and $74,783 (A-RE). CONCLUSIONS: There was a noteworthy difference in predicted CV incidence across the four equations; however, CE results were relatively stable. Consequently, choice of RE appears unlikely to significantly impact CE.