Purpose: Proton-pump inhibitors (PPIs) are frequently used to treat gastroesophageal reflux disease (GERD) in children, but recent evidence suggests a potential association between PPI treatment and some types of infections. The aim of this study was to assess the effectiveness of Lactobacillus rhamnosus GG (LGG) for the prevention of gastrointestinal and respiratory tract infections in children with GERD treated with PPI (omeprazol). Methods: Children younger than 5 years with GERD were assigned by a computer-generated list to receive LGG (109 colony-forming units) or placebo, twice daily, concomitantly with PPI treatment for 4–6 weeks; they were followed up for 12 weeks after therapy. The primary outcome measures were the percentage of children with a minimum of one episode of respiratory tract infection and the percentage of children with a minimum of one episode of gastrointestinal infection during the study. Results: Of 61 randomized children, 59 patients (LGG n=30; placebo n=29, mean age 11.3 months) were analyzed. There was no significant difference found between the LGG and placebo groups, either for the proportion of children with at least one respiratory tract infection (22/30 vs. 25/29, respectively; relative risk [RR] 0.85, 95% confidence interval [CI] 0.66–1.10) or for the proportion of children with at least one gastrointestinal infection (9/30 vs. 9/29, respectively; RR 0.97, 95% CI 0.45–2.09). Conclusion LGG was not effective in the prevention of infectious complications in children with GERD receiving PPI. Caution is needed in interpreting these results, as the study was terminated early due to slow subject recruitment.