Background: Thymic Hypoplasia (HT) in children is a cause of recurrent infections indicative of immunodeficiency. The present study aimed to evaluate the efficacy of Biomodulina T, a thymic polypeptide preparation, in pediatric patients with HT associated or not with cellular immunodeficiency. Methods: A non-controlled, Phase III clinical trial was conducted in children aged 1 to 5 years, including 60 patients, divided into two groups. Group I included 44 patients with HT not associated with cellular immunodeficiency and group II, 16 with cellular immunodeficiency. Patients were treated with Biomodulina T IM during two 4-week cycles with an intermediate 4-week rest period. Patients not reaching a normal thymus size at 16 weeks received a third cycle for 8 weeks. Results: Both groups of patients increased thymus size referred to baseline with no significant differences between them (P>0.05). The mean increase was 67% and 86.5% of patients concluded the treatment with a normal range thymus. Bacterial infections were reduced by 91.5% and viral infections by 80.7%. Consequently, antibiotic consumption was reduced. In patients with cellular immunodeficiency Biomodulina T induced a significant increase in CD4 +T lymphocytes (p<0.05). No significant differences were seen in CD8 +T cells, CD19 +B cells, and CD56 +NK cells. Serum IgA values were also significantly increased. Overall, 82.7% of patients were classified as better, coinciding with normalization of the thymus size and decreasing infections by at least 50%. Conclusions: Treatment of HT in children with Biomodulina T was clinically effective, regardless of the presence or not of cellular immunodeficiency.