Aim: To evaluate the platelet indices in differentiating reactive and clonal thrombocytosis. Study Design: Observational study Place and Duration of Study: Department of Pathology, Saveetha Medical College, Chennai, and the duration of study is one year. Methods: This is an observational study conducted at our college for a one-year duration. A total of 100 patients with thrombocytosis of platelet count over 4.5 lakhs/mm3 will be included in the study. The study sample consists of cases with thrombocytosis of over 4.5 lakhs. The utility of platelet indices Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW) for the differential diagnosis of thrombocytosis were analysed and assessed. Results: Out of the total 100 cases, 94 were reactive thrombocytosis, and 6 were confirmed to be clonal in origin. Infectious and reactive aetiology was significantly more compared to clonal thrombocytosis. Patients with reactive thrombocytosis showed a lower mean platelet volume and platelet distribution width compared to primary thrombocytosis. In reactive thrombocytosis, MPV ranged from 8.0 - 9.0 fl with mean MPV of 10.6 fl and PDW ranged from 8.4 – 10.1 % with mean PDW of 10.26 %. In clonal thrombocytosis, MPV ranged from 8.2 –1 1.1 fl with mean MPV of 9.5 fl and PDW range was 8.9 – 11.2 % with mean PDW of 10∙1%. Conclusions: The findings of our study favour a reactive cause in thrombocytosis when MPV and PDW are in the lower range and clonal causes had a high MPV and PDW in comparison to reactive causes.