Introductioncoronary artery disease (CAD) is one of the leading causes of death worldwide, only two thirds of cases can be explained by CAD´s classical risk factors. There is an increase in attention to homocysteine as a causal of CAD. In Palestine, CAD is more common than that in regional surrounding areas. Coronary artery disease is considered the leading cause of death in the West Bank, according to Palestinian Ministry of health annual reports. The study was conducted to determine the level of homocysteine in individuals with no history of CAD and to determine the relationship between CAD and total homocysteine levels and classical risk factors of CAD.Methodsour study is a hospital-based case-control study. A sample size of 84 cases and 81 controls were included in the study.Resultsthere is a statistically significant increase in plasma total homocysteine level in cases compared to controls (P=0.04) with Odds ratio= 2. There is also a statistically significant association between plasma total homocysteine levels and age of 50 years and above and male gender among both study groups (P= 0.002 and 0.007, respectively). The study showed no significant association between plasma total homocysteine level and the CAD´s classical risk factors among the case group measured in the study, which are diabetes mellitus, hypertension, and smoking (P=0.5, 0.1, and 0.5, respectively).Conclusionthere is a significant difference in homocysteine levels between case and control groups. Coronary artery disease patients have double homocysteine levels compared to those healthy individuals with OR= 2. Healthy Palestinian individuals have a homocysteine level that is lower than that of regional communities. Homocysteine levels increase with advanced age and male gender. There is no significant relation between hyperhomocysteinemia and diabetes mellitus, hypertension, and smoking.