- Background ST segment resolution (STR) is a strong predictor of outcome following thrombolysis. If failure of STR could be predicted on admission, better selection of treatment may be possible. Among patients given reperfusion, those with terminal QRS distortion (grade 3 ischemia) have larger infarcts, but the mechanism underlying this association is unclear. Whether grade 3 ischemia on admission can predict STR is unknown. Methods We studied 180 consecutive patients given thrombolysis for a first anterior acute myocardial infarction (AMI). Multiple variables available on admission were analyzed as predictors of STR at 1, 2, and 24 h and as predictors of the need for rescue percutaneous coronary intervention (PCI). Results Multivariate predictors of failure of STR were: for 1 h: extent of ST elevation (OR: 1.09 [1.01–1.18]); for 2 h: no previous use of beta-blockers (OR: 4.71 [1.56–13.98]) and grade 3 ischemia (OR: 6.77 [3.27–13.95]); for 24 h: previous use of aspirin (OR: 6.70 [1.31–34.01]) and grade 3 ischemia (OR: 29.44 [7.30–118.1]). Grade 3 ischemia had a strong positive predictive value for failure of STR at 1 and 2 h and was the strongest predictor of the need for rescue PCI. Conclusions Grade 3 ischemia on admission is the strongest independent predictor of failure to achieve myocardial reperfusion after thrombolysis. This association may underlie the larger infarcts associated with grade 3 ischemia. Other predictors of reperfusion failure are the extent of ST segment elevation, prior use of aspirin and no prior use of beta-blockers.