Diabetes mellitus (DM) is the greatest risk factor for coronary artery disease. In addition to a long duration of diabetes, the presence of peripheral arterial disease and smoking are strong predictors of abnormalities on myocardial perfusion scintigraphy (MPS). This study aimed to assess the impact of risk factors in diabetic patients on MPS results and compare them with those of non-diabetic patients in a nuclear medicine clinic. A retrospective cross-sectional study was performed through the analysis of the medical records of patients who underwent MPS in 2010–2019. A total of 34,736 medical records were evaluated. Analyzing the stress phase of MPS, DM patients required two-fold more pharmacological stimulation than nondiabetic patients for MPS. Factors that negatively impact the MPS results were also evaluated, and DM (33.6%), insulin therapy (18.1%), systemic arterial hypertension (69.9%), dyslipidemia (53%), sedentary lifestyle (83.1%), use of pharmacological stress (50.6%), typical chest pain (8.5%), and limiting angina during the test (1.7%) were significantly associated (p < 0.001) with test abnormalities