Introduction: Chest pain is a common presentation in the emergency department and physician office visits. Identifying coronary artery disease (CAD) as the cause of chest pain is essential for improving prognosis. The 2021 AHA/ACC guidelines do not advocate for testing in patients with low pretest probability (PTP <15%) of CAD. However, the pretest probability does not account for CAD risk factors. We sought to evaluate the yield of stress myocardial perfusion imaging (MPI) in patients with chest pain and low PTP of CAD in a population with a high prevalence of CAD risk factors. Methods: We reviewed all the patients referred to positron emission tomography from May 2011 to January 2022. Patients with chest pain and low PTP of CAD were included in the analysis. Patients with heart failure and valvular heart disease were excluded. Low PTP was defined as ≤15% on Juarez-Orozco classification. Moderate-severe ischemia is defined as ≥10% ischemic myocardium. Results: 2235 patients (age 54.2 ± 9.3 years, 23.8% males) with low PTP of CAD were included in the analysis. 303 (13.6%) of the cohort had ischemia out of which 100 (33%) patients had moderate-severe ischemia. Patients with ischemia had more prevalence of diabetes, hypertension, and hypercholesterolemia. The presence of two risk factors was associated with a higher likelihood of moderate-severe ischemia (OR = 2.2, 95%CI: 1.1 - 4.4, p=0.025) Conclusions: Ischemia is common among patients with low PTP of CAD and a high prevalence of risk factors. The presence of two risk factors is associated with a more than 2-fold increase in the risk of moderate-severe ischemia. Risk factors should be taken into consideration when deciding about further testing in this population. Further studies are needed to verify the prognostic value of testing in this population