While dihydropyridine calcium antagonists may be harmful in the immediate peri-infarction period, the effect of verapamil or diltiazem in these circumstances in uncertain. We utilized the GUSTO-1 formula to calculate the predicted 30-day mortality risk in a cohort of 352 patients with acute myocardial infarction presenting < 6 hours after onset of symptoms, with ECG changes consistent with eligibility for thrombolysis. All patients were treated with an intravenous bolus dose of verapamil followed by oral verapamil (240-360 mg/day) or diltiazem (180-360 mg/day), in the absence of specific contraindications. Predicted 30-day mortality risk was then compared with the actual 30-day mortality rate of the cohort. The actual 30-day mortality of the cohort was 3.7% (95% CI: 2.0,6.3); this was significantly lower than that predicted by the GUSTO-1 formula (7%). A similarly significantly lower mortality (7.5% vs 19.3%) was observed in a "high risk" subset of patients. Of the 13 patients who died, only 4 developed cardiogenic shock. It is concluded that verapamil and diltiazem can be administered safely in a selected patients with evolving acute transmural myocardial infarction. While the current data suggest that this form of treatment may be beneficial, definitive conclusions in this regard should await further randomized studies.