Abstract Funding Acknowledgements Type of funding sources: None. Introduction In general, most people spend their day in a non-fasting state. Hence, it is suggested that the changes in atherosclerosis happen mainly under the influence of non-fasting lipids. Up to date, the studies in the postprandial state were primarily performed on healthy subjects. Aim This exploratory, cross-sectional study investigates the change in lipid profile, in biomarkers of inflammation, as well as markers of platelet activation in patients with different cardiovascular risk profiles in the postprandial state. Methods The studied population consists of 66 patients with different cardiovascular risk: patients with a history of chronic coronary syndrome (CCS) and diabetes mellitus type 2 (DM2) (n=20), CCS without DM2 (n=25), and a healthy control group (n=21). Lipid variables and markers of platelet function were assessed during the fasting state (baseline) and three and five hours after a standardized fat meal using a standardized oral fat tolerance test (OFTT), a milkshake with 90g of fat. Platelet activity was measured with the Multiplate Assay using adenosine diphosphate (ADP), arachidonic acid (ASPI) and thrombin-receptor activating peptide (TRAP) as stimulants. Results Patients with CCS and DM2 were significantly older and had the highest BMI. All patients with CCS were on acetylsalicylic acid, and 95% of CCS patients were on high-dose statins. HDL-c decreased significantly during the OFTT, with a peak after five hours (3.46±0.4 mg/dL, p<0.001). Triglycerides (TG) increased significantly during the OFTT, with a peak after five hours (130.2 ± 14.5 mg/dL, p<0.001) irrespective of the group. All other variables of the lipid profile remained stable during the OFTT. The absolute leucocyte and neutrophile count and the neutrophile to lymphocyte ratio (NLR) increased significantly during the OFTT in the whole study population, whereas the absolute lymphocyte count increased significantly only in the control group. A significant increase in platelet activity during OFTT was shown in the control group by the increased absolute platelet count, increased reticulated thrombocytes, and increased platelet reactivity measured by the ASPI and TRAP tests, respectively. There was no significant change in the markers of platelet activity during the OFTT in patients with CCS with/without DM2. Conclusion This study showed that a standardized fatty meal changes HDL-c and TG concentrations and leads to an increased postprandial inflammation response irrespective of the cardiovascular risk and to increased platelet activity in healthy subjects, while there was no increase in platelet activity in higher-risk CCS patients.