Background: Acute myocardial infarction (MI) can occur in patients with previously normal stress myocardial perfusion imaging (MPI). It is not known whether the prognosis of these patients differ from those with MI who had an abnormal MPI on an earlier testing. The aim of this study was to compare the outcome of patients who sustained a MI during follow-up after stress MPI based on the presence or absence of perfusion abnormalities on the earlier test. Methods: We studied 109 patients (age 62 +/- 11 years, 73 men) who developed MI 2.1 +/- 2.7 years after exercise or dobutamine stress Tc-99m tetrofosmin MPI. Subsequently, a follow-up was done for the occurrence of death during or after the acute event. Results: Myocardial perfusion was normal in 31 patients and was abnormal in 78 (45 had reversible defects). During a mean follow-up of 3.1 +/- 2.4 years after MI, death occurred in 35 (32%) patients. The death rate was 19% in patients with previously normal versus 33% in patients with abnormal perfusion (P < 0.01). In a Cox model, independent predictors of death were age (risk ratio (RR) 1.06, 95% Cl: 1.02-1.10), heart failure (RR 2.7, Cl: 1.3-5.5), and abnormal MPI (RR 2.5, Cl: 1.3-4.5). Conclusion: Patients with a previously normal stress MPI are less likely to die after acute MI than patients who had an abnormal MPI.