Antibiotic resistance of Helicobacter pylori strains from 106 symptomatic children was evaluated according to EUCAST breakpoints and rate of multidrug resistance (MDR) was analyzed. Overall resistance rates were amoxicillin 7.5%, metronidazole 25.5%, clarithromycin 34.0% and ciprofloxacin 14.1%. There were no significant differences in resistance rates according to patients' age (2-6 and 7-18 years) and sex. Combined resistance rate was 19.8%, including double, triple, and quadruple resistance in 13.2% (14 strains), 5.7% (6) and 0.9% (1) of the strains, respectively. MDR was found in 5.9% (5/84) of the children with gastritis and in two of the four children with celiac disease. The MDR was present in three children aged 4-6 years and in four children aged 10-17 years. The total MDR rate (6.6%) in Bulgarian children in 2012-2021 was higher than those in other studies based on EUCAST breakpoints such as those in pediatric patients in Slovenia in 2011-2014 (3.8%), Lithuania in 2013-2015 (0%) and Spain in 2014-2019 (0%), although being lower than those (20.7% in the untreated and 47.0% in the treated children) in China in 2019. In brief, it is of concern that MDR can strongly limit the choice of H. pylori therapy of one out of fifteen Bulgarian children and that overall resistance to both metronidazole and clarithromycin can hinder the treatment of 15.1% of the pediatric patients. Susceptibility-guided tailored eradication therapy of H. pylori infection should be more frequently implemented in the symptomatic children to avoid risks of both the infection itself and multiple antibiotic treatments.  Kulcsszavak: Helicobacter pylori; children; antibiotic; resistance; multidrug