An elevated level of total plasma homocysteine has been associated with a higher risk of atherosclerosis and coronary heart disease. The aim of our research was to study the relation between homocysteine and myocardial infarction (MI) in young patients. We conducted a case-control study in Constanţa County, Romania including 61 patients, divided in two groups. The first group, the MI group, consisted of 28 patients, male (67.9%) and female (32.1%) aged less than 45 years who were consecutively admitted to the Intensive Coronary Care Unit of the Emergency County Hospital of Constanţa from September 1, 2017 to August 31, 2018 (12 months), with an established diagnosis of first acute MI. The second group, the control group, included 33 patients, male (75.8%) and female (24.2%) aged less than 45 years, with cardiovascular risk factors and/or stable angina pectoris that were consecutively addressed for ambulatory cardiac evaluation at the Outpatient Clinic of Emergency County Hospital of Constanţa during the same period. Fasting plasma homocysteine was determined in both groups, within 24 h after MI onset, respectively after first cardiac exam in the controls. High homocysteine was statistically confirmed to be a risk factor in the study group, especially in association with smoking, chronic kidney disease (CKD), and to a lesser extent with diabetes mellitus (DM) and hypertension. Data analysis was performed using IBM SPSS Statistics 23. The procedures used included descriptive statistics, parametric statistical tests (Independent sample t-test), non-parametric statistical tests [Chi-square test of the association, with the evaluation of odds ratio (OR)]; the significance level used in the analysis (P-value) was 0.05. After adjusting for variables, our study results pointed out a strong association between plasma homocysteine and first acute MI among young patients, emphasising plasma homocysteine as a possible risk factor for myocardial infarction.