Background: Dengue fever is one of the most important emerging infectious diseases constituting important contribution in global burden of disease. Platelet transfusion is required in the patients when they develop Dengue Hemorrhagic Fever (DHF) or thrombocytopenia below 20,000/ cu.mm without hemorrhage. Serial platelet counts are used to monitor the patients. In this study we investigated whether Mean Platelet Volume (MPV) could be used as a tool to predict development of significant thrombocytopenia, DHF and Dengue Shock Syndrome (DSS). This may help in triage of high-risk patients and readiness of the care-givers for platelet transfusion when required. Methods: In this prospective study done in IIMSAR, Halides, 100 cases of dengue were included. In those patients who developed thrombocytopenia < 20,000/cu.mm, the MPVs prior to development of this significant thrombocytopenia, were compared with the mean of the MPVs of all the patients under the study. Statistical analysis was done using t-test. Results: On the previous day on which platelet count was < 20,000/cu.mm, mean MPV was significantly low (p value < 0.0001) compared to the mean of MPVs of all the patients. Conclusion: Serial MPV monitoring can be used to predict significant thrombocytopenia.