To investigate the antiischemic efficacy of intravenously administered diltiazem, 42 patients were randomly allocated to receive placebo or active treatment before 1-vessel percutaneous transluminal coronary angioplasty (PTCA). The development of myocardial ischemia was studied using subjective (pain) and objective (electrocardiography) parameters. Pretreatment with intravenous diltiazem resulted in a significantly delayed onset of ischemic pain and ST-segment elevation; these variables also returned to baseline earlier after balloon deflation. Thus, intravenous diltiazem prevents or delays the onset of myocardial ischemia during repetitive transient coronary occlusions; improvement of the myocardial blood flow distal to the coronary occlusion or impedance of calcium entry into the ischemic cell are considered as possible mechanisms. Because PTCA is increasingly used in patients with poor left ventricular function and more extensive disease, and because recent evidence suggests that better PTCA results could be obtained by the use of longer inflation times, the addition of diltiazem to the classic armamentarium could be beneficial.