The present study aimed to retrospectively evaluate the usefulness of cell counter-based parameters and formulas in beta-thalassemia trait (BTT) detection. The study included 170 BTT cases (hemoglobin [Hb]A(2) >4.0% [0.04]) and 30 non-BTT cases (HbA(2), 2.3%-3.5% [0.02-0.04]). Depending on the hemoglobin level and iron deficiency, the BTT group was further classified into classic BTT (n = 112) and BTT with iron deficiency anemia (n = 58). The RBC count, MCH, MCV, RDW, and Shine and Lal, Mentzler, Srivastava, England and Fraser, Ricerca, and Green indexes were applied. For the first time in the population of India, these 10 cell counter parameters and manual formulas were compared with high-performance liquid chromatography-derived HbA2 levels for deriving a cost-effective alternative method; and receiver operating characteristic curves were applied. We found that the Shine and Lal, Srivastava, and Mentzler indexes, MCV, and MCH have better discriminative function than the RBC count and red cell distribution width and their related formulas.