Background/objectives We evaluated whether atherosclerotic changes associated with MetS in Australian Aboriginals are reversible in childhood. In addition, we investigated whether heightened inflammation is mediating the adverse effects of MetS. Methods The study cohort comprised of 351 children from the Aboriginal Birth Cohort Study (a longitudinal study based in the Northern Territory of Australia) aged 9-13 years at baseline examination who were followed up 6 years later. MetS was defined by at least three of the following parameters within the extreme sex- and age-specific quartile: highest quartile for waist circumference, blood pressure, triglycerides, and glucose, and lowest quartile for HDL-cholesterol. Carotid intima-media thickness (IMT) and C-reactive protein (CRP) were assessed at follow-up. Results Individuals with MetS at baseline or follow-up had increased carotid IMT at follow-up (mean ± SEM 539 ± 3 vs. 561 ± 8 μm, P = 0.007; and 537 ± 3 vs. 567 ± 8 μm, P < 0.0001 respectively). In combined analyses from baseline and follow-up studies, those individuals with MetS only at baseline had partially improved vascular status; their IMT was not significantly increased compared to those without MetS at both time-points (534 ± 3 vs. 550 ± 10 μm, P = 0.09). At the follow-up examination, MetS status was associated with increased IMT levels only among individuals with CRP levels above the median (≥ 2.1 mg/l) (536 ± 5 vs. 573 ± 9 μm, P < 0.0001, P for interaction 0.01). Conclusions MetS in childhood is associated with subclinical atherosclerosis in an Australian Aboriginal population and the effects appear to be mediated by increased inflammation. The extent of atherosclerosis was partially reduced if metabolic status improved during the follow-up.