Introduction: Coronary risk factors (CRF) and acute coronary syndromes (ACS) are decreasing in developed countries but continue to be a major public health problem. The increased risk of recurrent cardiovascular events ACS are not fully explained by the conventional risk factors alone. This study examines the association of diet and depression as risk factors of ACS. Subjects and Methods: We used a case-control study design including 435 patients with ACS who were compared with 495 age-and gender-matched control subjects. Clinical, electrocardiographic, radiological and laboratory data were obtained in all the patients for confirmation of diagnosis by WHO and AHA criteria. Depression as risk factor of ACS was assessed by validated questionnaires. Western-type and Indo-Mediterranean type food intakes were assessed by food intake records for 7 days, noted in dietary diaries. Multivariate logistic regression analysis was conducted after adjustment of age, gender, and body mass index (BMI) to determine the association of risk factors with ACS. Results: The incidence of depression (19.8 vs. 6.3%, P < 0.001) and increased intake of Western-type foods were significantly more common among ACS cases compared to the control group. The consumption of Indo-Mediterranean foods and blood nitrite concentrations were significantly lower among ACS patients as compared to the control group. After adjustment for age and BMI, depression was positively and strongly associated with ACS (P < 0.001), as shown by odds ratios and their 95% confidence intervals. Depression (males: 0.33 (0.29-0.38)**; females: 0.29 (0.23-0.35)**) and Western-type foods intake (males: 0.44 (0.38-0.53)**; females: 0.47 (0.41-0.53)** were significantly and strongly associated with ACS (P < 0.001). Indo-Mediterranean food intake-0.46 (0.38-0.48)** and females-0.43 (0.37-0.47)* and blood nitrite (males: 0.61 (0.51-0.75)*; females: 0.58 (0.43-0.72)* were inversely and weakly associated with ACS (P < 0.02). A weaker positive association (P < 0.02) of angiotensin converting enzyme (males: 0.57 (0.46-0.68)*, females:-0.43 (0.37-0.47)* with ACS was also found. Conclusion: This study shows that depression, Western-type food consumption and high blood angiotensin converting enzyme were significant risk factors of ACS. Indo-Mediterranean type food intake and blood nitrite showed beneficial effects on risk of ACS. © 2018 Nova Science Publishers, Inc.