Objectives <p>Atherosclerosis, a chronic inflammatory condition characterized by arterial plaque buildup, contributes to cardiovascular disease-related morbidity and mortality. The Dietary Guidelines for Americans (DGA) inform nutrition policy, and the Healthy Eating Index (HEI) assesses diet quality based on its alignment with the DGA. This case-control study investigated HEI-2020 in newly diagnosed patients with atherosclerosis, compared to a healthy control group. Patients newly diagnosed with atherosclerosis comprised the case group, while gender- and age-matched volunteers served as the control group. Participants completed a validated 168-item food frequency questionnaire (FFQ). The Healthy Eating Index 2020 (HEI-2020) was calculated based on the FFQ data. Descriptive statistics and statistical tests such as the independent t-test and logistic regression were performed using SPSS software.</p> Results <p>One hundred and three newly diagnosed atherosclerotic patients and an equal number of healthy controls were included. A significant difference was found in the mean HEI-2020 score between the case and control groups (<i>p</i> = 0.029). Logistic regression analysis indicated that HEI-2020 was a predictive factor for atherosclerosis development (<i>p</i> = 0.031), even after adjusting for BMI and physical activity (<i>p</i> = 0.035). Therefore, we found that HEI-2020 was a predictor of atherosclerosis incidence.</p>