Previous experimental studies have clarified the effectiveness of intermittent coronary sinus occlusion or ICSO. We evaluated the clinical feasibility, safety and effectiveness of ICSO in the patients with acute myocardial infarction (AMI) who were treated with concomitant thrombolytic therapy. Implementation of ICSO was obtained in 76% of the eligible patients. Twelve patients with evolving anteroseptal infarction treated with ICSO + thrombolysis were compared with 12 patients with anterior AMI treated with thrombolysis alone. Baseline characteristics were comparable between the two groups. Adverse effects of ICSO on hemodynamics, hematologic parameters and ventricular arrhythmias were not detected. Enzymatic infarct size, myocardial lactate metabolism in the acute phase, and left ventricular wall motion and Tl-201 perfusion defect at follow-up in ICSO group were slightly improved compared with controls.