When screening for α‐thalassemia in children, adult cut‐offs for mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) are generally applied to guide genetic evaluation. However, the normal ranges for MCV and MCH are lower in children than in adults, so we hypothesized that using age‐matched cut‐offs could lead to a more rational diagnostic strategy. The aim of this study was to evaluate if age‐matched cut‐offs could be applied advantageously. Data on children referred to a hemoglobin fractionation at the Department of Clinical Biochemistry, Aarhus University Hospital between 2016–2021 were identified in the laboratory information system. α‐globin gene (HBA1/HBA2) genotyping was performed using multiplex gap‐polymerase chain reaction. A total of 387 children were identified. HBA1/HBA2‐genotyping was performed in 207 children (53%), and α‐thalassemia was diagnosed in 47 children (23%) with −α3.7/αα being the predominant genotype (13%). We found that 23 children had MCV and MCH levels in the normal age‐matched range, and two of these children (9%) were α+ thalassemia carriers with three functional α‐globin genes. Using age‐specific cut‐off levels resulted in a reduction of 23 (11%) genotypes performed. In conclusion, applying age‐matched cut‐offs for MCV and MCH when screening children for α‐thalassemia lead to 11% fewer genotypes performed while 9% carriers of α+ thalassemia (of the medically innocuous genotype −α3.7/αα) would have been overlooked.