To better understand the factors predisposing a patient to death after elective percutaneous transluminal coronary angioplasty (PTCA) and to gain insight into indications for high-risk PTCA both with and without adjunctive use of support devices, the outcomes of 8,052 consecutive procedures were reviewed. Death occurred after 32 procedures (0.4%) and was directly related to coronary artery closure in 26 (81%) of these cases. Left ventricular failure due to vessel closure at the dilated site, the most common cause of death, was independently correlated with female sex (p less than 0.001), "jeopardy score" (p less than 0.001) and PTCA of a proximal right coronary artery site (p = 0.002), but not with left ventricular ejection fraction or presence of multivessel disease. Right ventricular failure after closure of the proximal right coronary artery, and left main coronary dissection accounted for the majority of the remaining deaths. Systolic blood pressure immediately after coronary artery closure was also closely correlated with jeopardy score, and cardiogenic shock was frequent in women with scores greater than or equal to 3.5 and in men with scores greater than or equal to 5.0. These data highlight the superiority of the jeopardy score versus ejection fraction in the determination of risk, stress the importance of gender in determining outcome and point to the need for better means of right ventricular protection from severe ischemia. Therefore, an initial framework for rational use of PTCA and support devices in the high-risk setting is established.