Aims The objective of the study was to determine the mean platelet volume (MPV) and platelet distribution width (PDW) in subjects with type 2 diabetes mellitus (type 2 DM) compared to subjects without type 2 DM and their correlation with fasting blood glucose, glycosylated hemoglobin (HbA1c), and duration of type 2 DM respectively. Materials and methods A prospective analytical case—control study was conducted involving 50 subjects with type 2 DM and 50 subjects without type 2 DM. The mean and standard deviation were estimated for both the groups separately and independent Student's “t”-test was used for evaluating the significant difference. The statistical evaluation was carried out at 95% confidence level. Results Mean MPV and PDW in case group was significantly higher compared to control group (p < 0.005). Fasting blood glucose, HbA1c, and duration of type 2 DM did not significantly alter MPV or PDW. Conclusion The study concludes that MPV and PDW are significantly increased in patients with type 2 DM compared to patients without type 2 DM. Platelet volume indices are an important, simple, and cost-effective tool that should be used and explored extensively, especially in countries, such as India, for predicting the possibility of impending acute vascular events in patients with type 2 DM. Clinical significance This analytical method helps us to use MPV and PDW as early markers of vascular thrombosis. How to cite this article Bhanukumar M, Ramaswamy PKH, Peddi NK, Menon VB. Mean Platelet Volume and Platelet Distribution Width as Markers of Vascular Thrombosis in Type 2 Diabetes Mellitus. J Postgrad Med Edu Res 2016;50(3):127-131.