BACKGROUND: The frequency of abnormal stress single-photon emission computed tomography myocardial perfusion imaging (MPS) has decreased over the past decades despite an increase in the prevalence of cardiovascular risk factors. This study evaluated the temporal trend of abnormal stress MPS and its relationship with risk factors in a cohort of Italian subjects. METHODS: We included all patients who underwent clinically indicated stress MPS at our academic center between January 2006 and December 2017. Patients were assessed for change in demographics, clinical symptoms, risk factors, and frequency of abnormal and ischemic MPS. RESULTS: A total of 8,886 stress MPS studies were performed (3,350 abnormal). Age, male gender, diabetes, smoking, and angina were independent predictors of abnormal MPS. There was a slight decline in the frequency of abnormal (from 39 to 36%, P < 0.05) and ischemic (from 25 to 22%, P < 0.01) MPS during the study period, while the percentage of patients with hypertension, hypercholesterolemia, smoking, and angina increased. The Cochran-Mantel-Haenszel test indicates that the likelihood of having an abnormal MPS did not change over time for age, diabetes, smoking, and a history of coronary artery disease (CAD), increased for hypertension and hypercholesterolemia and decreased for male compared to female gender. CONCLUSIONS: In our cohort of Italian subjects, there was a slight temporal decline in the frequency of abnormal and ischemic MPS despite an increase over time in the prevalence of many cardiac risk factors. These results strengthen the need to develop more effective strategies for appropriately referring patients to cardiac imaging procedures.