Background/objectives The aim of the present work was to evaluate the association between the inflammatory potential of the diet and the 10-year cardiovascular disease (CVD) incidence in the ATTICA Study, and whether this is modified by the baseline presence or absence of metabolic syndrome (MetS). Methods During 2001–2002, 3042 healthy adults (1514 men and 1528 women) living in the greater area of Athens were voluntarily recruited to the ATTICA study. In 2011–2012, the 10-year follow-up was performed in 2583 participants (15% of the participants were lost to follow-up). Incidence of fatal or non-fatal CVD event was recorded using WHO-ICD-10 criteria and MetS was defined by the National Cholesterol Education Program Adult Treatment panel III (revised) definition. A proxy dietary anti-inflammatory index (D-AII) score computed using participants' diet records. Results The 10-year fatal or non-fatal CVD event rate was 157 cases/1000 participants. After adjusting for several confounding factors, an anti-inflammatory diet, as expressed by higher DII scores, was borderline associated with 10-year CVD incidence (OR3rd tertile vs. 1st tertile = 0.98, 95%CI: 0.96–1.01). This inverse association was also verified among participants without MetS at baseline (OR3rd tertile vs. 1st tertile = 0.97, 95%CI: 0.94–0.99), but not among participants with the MetS. Conclusions Results of the present work verified the protective effect of an anti-inflammatory diet towards the 10-year CVD incidence among participants without MetS. In contrast, the presence of MetS already at baseline seemed to impede this anti-inflammatory diet protective effect, which underlines the independent importance of MetS on CVD risk.