OBJECTIVES: Cardiovascular (CVD) mortality disparities between rural/regional and urban-dwelling residents of Australia are persistent. Unavailability of biomedical CVD risk factor data has, until now, limited efforts to understand the causes of the disparity. This study aimed to further investigate such disparities. DESIGN: Comparison of (1) CVD risk measures between a regional (Greater Green Triangle Risk Factor Study (GGT RFS, cross-sectional study, 2004-2006) and an urban population (North West Adelaide Health Study (NWAHS, longitudinal cohort study, 2004-2006); (2) Australian Bureau of Statistics (ABS) CVD mortality rates between these and other Australian regions; and (3) ABS CVD mortality rates by an area-level indicator of socioeconomic status, the Index of Relative Socioeconomic Disadvantage (IRSD). SETTING: Greater Green Triangle (GGT, Limestone Coast, Wimmera and Corangamite Shires) of South-Western Victoria and North-West Adelaide (NWA). PARTICIPANTS: 1563 GGT RFS and 3036 NWAHS stage 2 participants (aged 25-74) provided some information (self-administered questionnaire +/- anthropometric and biomedical measurements). PRIMARY AND SECONDARY OUTCOME MEASURES: Age-group specific measures of absolute CVD risk, ABS CVD mortality rates by study group and Australian Standard Geographical Classification (ASGC) region. RESULTS: Few significant differences in CVD risk between the study regions, with absolute CVD risk ranging from approximately 5% to 30% in the 35-39 and 70-74 age groups, respectively. Similar mean 2003-2007 (crude) mortality rates in GGT (98, 95% CI 87 to 111), NWA (103, 95% CI 96 to 110) and regional Australia (92, 95% CI 91 to 94). NWA mortality rates exceeded that of other city areas (70, 95% CI 69 to 71). Lower measures of socioeconomic status were associated with worse CVD outcomes regardless of geographic location. CONCLUSIONS: Metropolitan areas do not always have better CVD risk factor profiles and outcomes than rural/regional areas. Needs assessments are required for different settings to elucidate relative contributions of the multiple determinants of risk and appropriate cardiac healthcare strategies to improve outcomes.