Little research has examined the effects of high concentration, medium-duration smoke exposure on cardiovascular health. We investigated whether six weeks of exposure to smoke from the 2014 Hazelwood coal mine fire in Victoria (Australia), was associated with long-term clinical or subclinical cardiovascular disease approximately four years later, in adult residents of the towns of Morwell (exposed, n = 336) and Sale (unexposed, n = 162). The primary outcome was serum high sensitivity (hs) C-reactive protein (CRP). Blood pressure, electrocardiogram, flow mediated dilatation and serum levels of hs-troponin, N-terminal pro B-type natriuretic peptide and lipids were secondary outcomes. There was no significant difference in weighted median hsCRP levels between exposed and unexposed participants (1.9 mg/L vs. 1.6 mg/L, p = 0.273). Other outcomes were comparable between the groups. hsCRP was associated in a predictable manner with current smoking, obesity and use of lipid-lowering therapy. Four years after a 6-week coal mine fire, this study found no association between smoke exposure and markers of clinical or subclinical cardiovascular disease in exposed adults.