Background: Haemoglobin E-β thalassemia is a common haemolytic anaemia in South-East Asia. The patients show remarkable clinical heterogeneity-ranging from asymptomatic anaemia to severe transfusion dependence. There is no specific marker to predict the frequency of blood transfusion (BT) required by these patients.This study aims to find suchfactors like age of first BT, spleen size, levels of haemoglobin E (HbE), haemoglobin F (HbF) and the ratio of HbE to HbF. Materials and Methods: Fifty-eight HbE-beta thalassemia patients visiting the Thalassemia OPD and day care centre of a tertiary care hospital were included in the study. They were grouped into 3 groups according to their age of first BT: group 1 had patients with first BT below 2 years old, group 2 had those with first BT at/ above 2 years old; those without any BT were in group 3. Hb was estimated by automated cell counter. HbE & HbF levels were quantified by High Performance Liquid Chromatography (HPLC). Results: Out of 58 patients, seven patients belonged to group1, 46 to group 2 and five to group 3. Group 1 patients had average spleen size>6 cm, lower levels of steady state Hb and low HbF% whereas group 2 had spleen size ≤6 cm, higher steady state Hb levels and a higher HbF%. Significant statistical differences were observed in steady state Hb levels, HbF levels and spleen size. Conclusion: The study highlights that MCV, levels of HbE & HbF and the ratio of HbE to HbF can be used as predictors of severity and transfusion requirement in HbE-β thalassemia patients.