Background: Patients with acute myocardial infarction (AMI) who are not eligible for thrombolytic therapy or primary coronary angioplasty are distinguished by advanced age, complicated medical histories, relatively frequent use of prior revascularization procedures, and worse outcomes than their counterparts who are eligible for reperfusion therapy. Methods and Results: The purpose of this randomized, controlled trial was to determine whether RheothRx, a hemorheologic agent, reduced myocardial infarct size and improved left ventricular function in patients who had suspected AMI at the time of hospital admission and were not eligible for reperfusion therapy. Patients were randomly assigned to RheothRx (n = 97) or placebo (n = 99). Patients in the two groups were similar with respect to age, sex, medical history, and clinical presentation. Enzyme evidence of AMI was present in 69% of the treatment group and 70% of the placebo group. Infarct size measured before hospital discharge was similar in the two groups (14.1% ± 18.5% vs 11.7% ± 14.1%, p = 0.60), although left ventricular ejection fraction was lower in the treatment group (47 ± 14 vs 52 ± 11, p = 0.026). Hospital mortality rate was 11.3% and 7.1% in patients receiving RheothRx and patients receiving placebo, respectively (p = 0.30). There was a higher occurrence of acute renal dysfunction in the RheothRx group (12% vs 2%, p = 0.005). Because of changes in drug dosage necessitated by the occurrence of acute renal dysfunction, the trial was stopped. Conclusions: In this study of patients who had suspected AMI and were not eligible for thrombolytic therapy, RheothRx did not decrease infarct size or favorably alter outcome. The need for effective treatment for this large patient population remains largely unmet. (Am Heart J 1998;135:797-804.)