A higher dietary inflammatory index (DII®) score is associated with inflammation and incidence of coronary heart disease (CHD). We hypothesized that a Mediterranean diet (MedDiet) intervention would reduce DII score. We assessed dietary data from a randomized controlled trial comparing 6-month MedDiet versus low-fat diet intervention, in patients with CHD. We aimed to determine the DII scores of the prescribed diets' model meal plans, followed by whether dietary intervention led to lower (i.e., more anti-inflammatory) DII scores and consequently lower high sensitivity C-reactive protein (hs-CRP) and interleukin-6 (hs-IL-6). DII scores were calculated from 7-day food diaries. The MedDiet meal plan had a markedly lower DII score than the low-fat diet meal plan (−4.55 vs. -0.33, respectively). In 56 participants who completed the trial (84% male, mean age 62 ± 9 years), the MedDiet group significantly reduced DII scores at 6 months (n = 27; −0.40 ± 3.14 to −1.74 ± 2.81, P =.008) and the low-fat diet group did not change (n = 29; −0.17 ± 2.27 to 0.05 ± 1.89, P =.65). There was a significant post-intervention adjusted difference in DII score between groups (compared to low-fat, MedDiet decreased by −1.69 DII points; P =.004). When compared to the low-fat diet, the MedDiet non-significantly reduced hs-IL-6 (−0.32 pg/mL, P =.29) and increased hs-CRP (+0.09 mg/L, P =.84). These findings demonstrated that MedDiet intervention significantly reduced DII scores compared to a low-fat diet. However, in this small cohort of patients with CHD this did not translate to a significant improvement in measured inflammatory markers. The effect of improvement in DII with MedDiet should be tested in larger intervention trials and observational cohorts.