Objectives. We addressed the question whether in patients with cardiac chest pain referred for stress myocardial perfusion scintigraphy, Tc-99m MIBI SPECT stress imaging should always be followed by a rest imaging procedure. Background. Using Tc-99m MIBI imaging a stress-rest sequence is usually performed implying that the resting study always follows the stress study irrespective of the results of the stress study. As a normal stress study would eliminate a subsequent resting study, it appears desirable to potentially define certain subsets of patients in whom a normal stress study can be expected in order to determine a more selective referral approach to the nuclear medicine department. The consequences of such a more streamlined approach would less impose on the logistics of the department of nuclear medicine, with decrease of investigation time, radiation dose, and costs in a time of retrenchment in the medical sector. Methods. A consecutive series of 460 patients (mean age 58.2 years) was studied who were stratified to 269 patients without prior myocardial infarction, and to 191 patients with documented evidence of a previously sustained mycoardial infarction. All patients underwent Tc-99m MIBI SPECT imaging according to a two-day stress-rest protocol. Results. Patients with and without a previous myocardial infarction showed suboptimal overall predictive accuracies for the exercise electrocardiograms (58% and 60%, respectively). In the total group of 460 patients, 94 (20%) patients showed a normal stress-rest Tc-99m MIBI SPECT; this occurred in 86/269 (32%) patients without a previous myocardial infarction and in only 8/191 (4%) patients with a previous myocardial infarction. Conclusions. Patients with a stress defect at Tc-99m MIBI SPECT imaging should always undergo a resting SPECT study irrespective of the clinical and stress electrocardiographic findings. As patients without a previous myocardial infarction had a normal stress SPECT study in almost one-third (32%) of patients compared to only 4% in patients with a previous myocardial infarction, it may be useful to employ different referral and imaging strategies i.e. a stress-only versus a stress-rest procedure. To schedule referring patients differently according to the presence or absence of a previously sustained myocardial infarction may be cost-saving, less demanding for the nuclear medicine personnel, and patient-convenient. In addition, a stress-only imaging procedure reduces radiation exposure to the individual patient.