Evaluation of red blood cell (RBC) morphology is an important first step in the differential diagnosis of hereditary hemolytic anemia. It is, however, labor intensive, expensive, and prone to subjectivity. To improve and standardize the analysis of RBC morphology as a screening tool in the diagnosis of hereditary hemolytic anemia, we studied its automated analysis by digital microscopy (DM). Blood from 90 patients with hereditary hemolytic anemia and 32 normal control subjects was analyzed by the CellaVision DM96 Digital Microscope. All hemolytic RBC abnormalities could be distinguished by the presence of at least one aberrant red cell type. In particular, the percentage of microcytes was highly sensitive and specific (AUCROC =0.97) for RBC membrane disorders, and a cut-off of 5.7% microcytes was calculated to be optimal to distinguish patients from healthy controls. Subgroup analysis of patients with RBC membrane disorders revealed additional distinct differences according to the underlying gene defect. A number of cell types were significantly elevated in sickle cell anemia patients, such as polychromatic cells, macrocytes, and poikilocytes. The increase in helmet cells (AUCROC =0.96) and hypochromic cells (AUCROC =0.91) was specific for β-thalassemia, whereas patients with pyruvate kinase deficiency showed a significant increased polychromatic cells, macrocytes, and ovalocytes. Patients with hereditary xerocytosis showed significantly higher numbers of polychromatic cells, macrocytes, and target cells. DM holds a promise as a useful screening tool in the diagnosis of hereditary hemolytic anemia by detecting and quantifying distinct morphological changes in RBCs in patients with various forms of hereditary hemolytic anemia.