Acute myocardial infarction (AMI) of the inferoposterior wall is due to occlusion of the right coronary artery (RCA) or the left circumflex (LCx) coronary artery. The outcome of patients depends mainly on the culprit artery. Therefore, the presumptive prediction of a culprit artery based on the electrocardiogram recorded at admission is of clinical importance. The aim of this study was to develop a sequential algorithm based on the “ups and downs” of the ST segment in different leads to predict the culprit artery (RCA vs LCx) in cases of inferoposterior AMI. We analyzed electrocardiographic and angiographic findings of 63 consecutive patients with an evolving AMI with ST elevation in the inferior leads (II, III, and aVF) and a single-vessel occlusion. Specificity, sensitivity, and positive and negative predictive values of different electrocardiographic criteria (ups and downs of the ST segment) were studied individually and in combination to find an algorithm that would best predict the culprit artery. The following electrocardiographic criteria were included in the 3-step algorithm: (1) ST changes in lead I, (2) the ratio of ST elevation in lead III to that in lead II, and (3) the ratio of the sum of ST depression in precordial leads to the sum of ST elevation in inferior leads [(∑ ↓ST in leads V₁ to V₃)/(∑ ↑ST in leads II, III, and aVF)]. Application of this sensitive algorithm suggested the location of the culprit coronary artery (RCA vs LCx) in 60 of 63 patients (>95%). The few patients in whom this algorithm did not work were those with a very dominant LCx that presented ST depression of ≥0.5 mm in lead I. In conclusion, careful sequential analysis of an electrocardiogram of an inferoposterior AMI with ST elevation may lead to the identification of a culprit artery.