AIM: Recurrent respiratory infections (RRI) constitute a social problem for both the pharmaco-economic impact and the burden for the family. Pidotimod is a synthetic immunostimulant. The aim of this study was to evaluate the effects of pidotimod on RRI prevention in children. METHODS: Globally, 100 children (49 males, mean age 4.7 ± 1.2 years) with RRI were enrolled in the study. At baseline, children were randomly assigned to the treatment with pidotimod 400 mg/die or not for two months. Children were visited at baseline, after 30 (T1) and 60 (T2) days, and at follow-up (120 days; T3). Number of children with upper and lower airways symptoms, medications use, school attendance, and paediatric visits for RRI were evaluated. RESULTS: Pidotimod treatment was able of significantly reducing the number of children with upper and lower airways symptoms, and medications use, increasing school attendance, and reducing pediatric visits for RRI. CONCLUSION: This study provided the evidence that pidotimod may be able of preventing RRI in children.