Background: To find out the prevalence of hemoglobinopathies by screening large population in West Bengal from Eastern India. Materials and Methods: A total of 50,487 subjects are screened for hemoglobinopathies from June 2010 to August 2013. A 2.5 ml of venous blood samples were collected in the tri-potassium EDTA vacuum container from each subject and tested with automated blood cell counter (Sysmex KX21) for red cell indices. Diagnosis of hemoglobinopathies was done by VARIANTTM (Bio-Rad Laboratories, Hercules, CA, USA) high performance liquid chromatography (HPLC). Results: Out of 50,487 cases, 44,620 (88.38%) had normal and 5,867(11.62%) showed abnormal hemoglobin fractions on HPLC. Of these, 5,180(10.26%) were heterozygotes (traits) and 687(1.36%) cases were either homozygotes or compound heterozygote for different types of hemoglobinopathies. The following hemoglobinopathies were present: β-thalassemia trait 6.61%, HbE trait 2.78%, sickle cell trait 0.56%, HbD-Punjab trait 0.21%, β-thalassemia major 0.73%, HbEE 0.05%, compound heterozygosity for HbE-β-thalassemia 0.42%, and HbS-β-thalassemia 0.15%. Conclusion: Among the hemoglobinopathies, β-thalassemia trait (6.61%) and HbE trait (2.78%) are prevalent in rural Bengal.