A healthy diet is dominant in cardiovascular disease (CVD) prevention. Inflammation is pivotal for CVD development. This study aimed to evaluate the association between the pro-inflammatory diet and the CVD risk. This cross-sectional study involved 10,138 Fasa adult cohort study participants. After excluding participants with missing data, the Energy-Adjusted Dietary Inflammatory Index (E-DII) was calculated to assess the inflammatory potential of diet using the recorded Food Frequency Questionnaire. Framingham risk score (FRS) was used to predict the 10-year risk of CVD. The association between E-DII and high risk for CVD was investigated using multinominal regression. After exclusion, the mean age of studied individuals (n = 10,030) was 48.6 ± 9.6 years, including 4522 men. Most participants were low risk (FRS <10%) for CVD (87.6%), while 2.7% of them were high risk (FRS ≥20%). The median FRS was 2.80 (1.70, 6.30). The E-DII ranged from -4.22 to 4.49 (mean E-DII = 0.880 ± 1.127). E-DII was significantly associated with FRS. This result persisted after adjusting for confounding factors and in both genders. This study revealed that the pro-inflammatory diet significantly increases the CVD risk. Consequently, reducing the inflammatory potential of diet should be considered an effective dietary intervention in CVD prevention.