Introduction: Myocardial F-18-FDG uptake is highly variable in oncologic whole body F-18-FDG PET/CT studies, ranging from quite intense to minimal distribution. Intense or heterogeneous myocardial F-18-FDG uptake is undesirable as it may interfere with the visual or quantitative evaluation of tumoral invasion and metastases in pericardium, myocardium or adjacent mediastinal structures. The diet, as well as many other factors, is assumed to influence the myocardial F-18-FDG uptake. Using a multivariate model, we tried to identify and predict the main factors influencing cardiac F-18-FDG uptake in patients referred for oncologic PET/CT evaluation. Methods: A total of 214 patients referred for oncologic F-18-FDG PET/CT scan were enrolled in our study. Patients were randomly allocated into two groups according to the diet they were instructed to follow during 24-hour period before imaging. One hundred and seven cases with a routine diet (RD) and the same number of patients with a low carbohydrate, high fat (LCHF) diet were included. All patients were fast 6 hours before imaging. Weight, height, blood glucose, heart rate, systolic and diastolic blood pressure were measured before radiotracer injection. Visual and quantitative analysis were done after imaging and the pattern of F-18-FDG uptake, as well as standardized quantitative value of cardiac uptake was determined for each case. Results: The frequency of undesirable cardiac F-18-FDG uptake in the LCHF group was significantly less than RD group (17% vs. 72%, p=30 as well as consumption of cardiotoxic chemotherapeutic agents, benzodiazepines and beta blockers were significantly associated with higher intensity of myocardial F-18-FDG uptake, while this undesirable finding was less evident in cases with diabetes mellitus. A multivariate logistic regression model including all of the mentioned variables revealed the diet was the only significant independent factor that predicted undesirable myocardial F-18-FDG uptake (p<0.001). Conclusion: LCHF diet 24 hours before PET/CT imaging is the only controllable independent factor influencing the intensity and pattern of myocardial F-18-FDG uptake and is recommended as an optimal preparation to suppress cardiac F-18-FDG uptake.