We evaluated whether a drug interaction between intravenous nitroglycerin or isosorbide dinitrate and heparin exists. Ninety-six patients with a diagnosis of acute myocardial infarction, unstable angina, or other thromboembolic disorders were divided into 3 groups: group I (control group, n = 35) received intravenous heparin alone; group II (n = 31) received combined intravenous nitroglycerin and heparin; and group III (n = 30) received combined intravenous isosorbide dinitrate and heparin. We determined the mean of 2 separate measurements of heparin dosage requirement, antithrombin III activity, and the dose of intravenous nitroglycerin or isosorbide dinitrate at the time that the ratio of activated partial thromboplastin time (aPTT) to baseline aPTT was 1.5 to 2.0. The mean therapeutic heparin dose standardized to total body weight of each group was 13.8, 15.4, and 15.5 U/kg/hour, respectively. At that time, patients were receiving intravenous nitroglycerin at doses of 58.8 ± 38.6 μg/min or intravenous isosorbide dinitrate at doses of 3.7 ± 2.0 mg/hour. The mean antithrombin III activity of each group was 22.2, 22.8, and 21.3 mg/dl, respectively. The overall results for groups I, II, and III, and results for the subgroup of patients with acute ischemic syndromes in those groups, did not differ significantly. The heparin dose did not show a significant correlation to the dose of intravenous nitroglycerin (r = −0.26, p > 0.05) nor to that of isosorbide dinitrate (r = 0.30, p > 0.05).