Primary screening for thalassemia carriers usually involves an accurate blood count using an automated blood cell analyzer. We analyzed the red cell and reticulocyte parameters from 200 samples of various types of thalassemias and identified the discrimination criteria for differential diagnosis. These were separated into four groups based on genotypes. These groups included α-thalassemia, β-thalassemia, β-thalassemia with Hb E and Hb E trait, which are the important target of thalassemia screening. To compare the effectiveness of the screening strategies, seven selected screening tools were compared, including MCV alone (cutoff <80 fL); MRV alone (cutoff <100 fL); SD-C-NR alone (cutoff >28.5); a combined MCV and MRV; a combined MCV and SD-C-NR; a combined MRV and SD-C-NR; and a combined MCV, MRV and SD-C-NR. The combination of MCV, MRV and SD-C-NR has highest sensitivity for discrimination in all thalassemia, β-thalassemia, α-thalassemia, Homozygous Hb E and Hb E trait groups as 99.5, 100, 98, 100 and 100 %, respectively. The effectiveness of the combination of MCV, MRV and SD-C-NR parameters in the present study was determined as the faster and higher sensitivity screening tool than the other methods, including simple, reliable, cost-effective, and using only one automated hematology analyzer, saving labor costs.