Background Down syndrome (DS) is a chromosomal disease in which all or part of a third copy of chromosome 21 is present. From the age of 6–9 months postnatal, endogenous growth hormone induces the production of insulin-like growth factor 1 (IGF-1), which has a significant influence on development. As a result, when growth hormone takes over as the primary regulator of development, the growth retardation associated with DS becomes more apparent. Aim The study’s purpose was to compare IGF-1 levels in children with DS to those in healthy children. Patients and methods This prospective cross-sectional research was conducted on 20 children with DS as the study group who attended the outpatient clinic of the Tanta University Pediatric Department’s Genetics Unit. Twenty healthy normal children with matched age and sex served as the control group. All included children were given a full history, clinical examination, and blood IGF-1 test. Results Serum levels of IGF-1 were considerably lower in children with DS (122 ± 83.3 ng/ml) when compared with healthy controls (169.4 ± 33.3 ng/ml). The median IGF-1 levels were significantly lower in the DS patient group (2–6 years) than that in the age group 7–12 years (60.4 vs. 153, respectively). IGF-1 was significantly positively correlated with age and BMI. Conclusion IGF-1 level in children with DS was substantially lower than that in healthy children, especially in the age group 2–6 years. Moreover, IGF-1 positively correlated with age and BMI.