Background: The most common causes of microcytic hypochromic anemia are iron deficiency anemia (IDA) and the beta-thalassemia trait (β-TT). The aim of the work is to compare the validity of the various simple indices to differentiate between iron deficiency anemia and β-thalassemia trait. Subjects and methods: A total of 2000 individuals were screened, by complete blood picture, measurement of serum iron, serum ferritin and hemoglobin separation; 224 patients were detected as having hypochromia and microcytosis.Among them 166 cases were IDA and 58 cases were β-TT. We calculated 11 discrimination indices. The number of correctly identified cases were determined, sensitivity, specificity, positive and negative predictive value and Youden's index (YI) of each discrimination index was calculated. Results: The percentage of correctly diagnosed patients is highest for Matos and Carvalho index (MCI) (95.5%) which is closely followed by Red cell distribution width index (RDWI) (93.7%). The third high index was Green and King (GKI) (91.9%). Sensitivity, specificity of MCI for detection of IDA was found 98.8%, 87.9% respectively. For β-TT, sensitivity and specificity was found 86.2% and 98.8% respectively. The YI of MCI was found 85.9%. It is followed by RDWI; its sensitivity and specificity for detection of IDA was found 97.6%, 85.3%. For β-TT, sensitivity and specificity was found 82.7% and 97.6% respectively. The YI of RDWI was 81.6%. Conclusion: Matos and Carvalho index and RDWI are easily available automated cell-count-based indices coming out as good discriminator between IDA and β-TT in our study.