Cardiac allograft vasculopathy is a major cause of mortality in heart transplant recipients. The aim of this study was to assess the prognostic value of stress myocardial perfusion imaging in heart transplant recipients. We studied 166 patients (age 54 +/- 10 years, 140 men) by symptom-limited bicycle exercise or dobutamine (up to 40 microg/kg/min) stress myocardial perfusion imaging 7.4 +/- 2.5 years after heart transplantation. An intravenous dose of 370 MBq of technetium-99m tetrofosmin was injected at peak stress and 24 hours after the stress test. An abnormal test was defined as reversible or fixed perfusion defects. Perfusion abnormalities were detected in 55 patients (33%). During a median follow-up of 2.5 years, 54 deaths (33%) occurred, 16 of which were due to cardiac causes. The incidence of perfusion abnormalities was higher in patients with subsequent cardiac death than in patients without subsequent cardiac death (69% vs 29%, p = 0.01). In an incremental multivariate Cox analysis, cardiac death was not predicted by age, gender, duration of transplantation, number of rejection episodes, or cytomegalovirus infection. In the next step, stress test parameters were added. The peak rate-pressure product was the only significant predictor at this step (risk ratio 0.84, 95% confidence interval 0.73 to 0.97, chi-square 7.7, p = 0.006). In the final step, the presence of abnormal myocardial perfusion was an independent predictor of cardiac death (risk ratio 3.5, 95% confidence interval 1.6 to 11.7, chi-square 4.7, incremental to clinical and stress test variables, p = 0.01). It is concluded that stress myocardial perfusion imaging with technetium-99m tetrofosmin single-photon emission computed tomography provides incremental data for the prediction of cardiac death in heart transplant recipients.