INTRODUCTION Many risk factors can affect depression and coronary disease, these including physiological and psychological risk factors (such as personality traits). OBJECTIVES Our objectives were to examine whether personality factors (The Five-Factor Model) can predict depression score in the depressed and coronary heart disease (CHD) individuals compared to that of healthy subjects. MATERIALS AND METHODS To achieve the above objectives, 100 depressed (Mean=35.90 years, SD=10.59 years), and 100 CHD (Mean=46.42 years, SD=12.52 years), patients and 100 healthy subjects (Mean = 37.97 years, SD =12.49 years) were selected by convenience sampling method. To compare the three groups of participants, ANOVA test was used. Stepwise Multiple Regression Analysis was used to identify the variables that most closely predict the perceived stress and depression scores. Pearson's Correlation Co-efficient was used to examine the correlation between variables. RESULTS In Neuroticism, the CHD patients had significant highest scores, followed by depressed patients. The healthy group had the least scores. In case of Extraversion, Openness and Agreeableness, healthy participants had significant higher scores followed by the depressed and CHD patients. Only in conscientiousness factor, Depressive and CHD groups had statistically less scores compared to the healthy group. Also, high Neuroticism and Age, and low Extraversion were significant protective factors for depression Scores of CHD patients, while high Neuroticism and low Extraversion function as predictors in the depressed and healthy groups. CONCLUSION The effects of Neuroticism and Extraversion on depression have been reported as inconsistent across previous studies. This study indicates that, older CHD individuals with high Neuroticism and low Extraversion scores are more vulnerable for depression.