There is increasing evidence that inflammation plays an important role in atherosclerosis. Such inflammation is likely related to the presence of infectious organisms. Hence, we examined whether the use of antibiotic drugs decreases the risk of first-time myocardial infarction (MI). We identified 6737 cases of first-time hospitalization for MI, and 67,364 age- and gender-matched, population-based controls during 1991-2002, using data from the County Hospital Discharge Registry and the Civil Registration System of North Jutland County, Denmark. All prescriptions for antibiotics prior to the hospitalization for MI were identified through a prescription database. Conditional logistic regression was used to estimate odds ratios (OR) associated with antibiotic use, adjusted for potential confounding factors including previous discharge diagnoses of hypertension, chronic bronchitis and emphysema, alcoholism, liver cirrhosis, or diabetes mellitus and prescriptions for anti-hypertensive drugs, antidiabetic drugs, lipid-lowering agents, high-dose aspirin, platelet inhibitors, oral anticoagulants, or hormone replacement therapy. The use of any one type of antibiotic in the 3 years before hospitalization was not associated with a decreased risk of MI; the adjusted ORs with corresponding 95% confidence intervals were 1.07, 1.00-1.14 for penicillins; 1.15, 1.00-1.33 for macrolides; 0.95, 0.65-1.39 for tetracyclines; 1.25, 0.84-1.87 for quinolones; and 0.95, 0.80-1.12 for sulfonamides. A slight increase in the risk of MI was seen with the use of more than one type of antibiotic in the preceding 3 years (OR = 1.17, 95% CI = 1.09-1.27). Our findings do not support the hypothesis that the use of antibiotics is associated with a lower risk of first-time MI.