Background. Research regarding the optimal therapeutic approach to Helicobacter pylori infection in children is ongoing. There is no consensus as to duration of treatment or second-line therapy. The purpose of this study was compare the efficacy of 7-day and 14-day triple therapies and report the results of second-line quadruple therapy in children. Methods. A total of 275 consecutive H. pylori-infected patients were enrolled into two groups. Group 1 (n = 180) received triple therapy with 14 days of amoxicillin and clarithromycin and 21 days of proton pump inhibitor. Group 2 (n = 95) received triple therapy including 7 days of amoxicillin and clarithromycin with 21 days of proton pump inhibitor. Subsequently, 89 patients not responding to the triple therapies received quadruple therapy comprising omeprazole (14 days), bismuth subcitrate (7 days), doxycycline (7 days), and metronidazole (7 days). Eradication was evaluated by 13 C-urea breath test. Results. The per-protocol eradication rates in groups I and 2 were 60.5 % and 55.8 %, respectively (P = 0.44). In the second interview with 227 patients, severe symptoms were reported to have disappeared in 59% and decreased notably in 34.8%. Helicobacter pylori was eradicated in 66.7% of patients at the end of the quadruple therapy. In the third interview with 75 patients, severe symptoms had decreased in 38.6% and disappeared in 56%. Conclusions. The different duration of the two treatment regimens had no impact on eradication rates. Furthermore, quadruple therapy was necessary to achieve H. pylori eradication after triple therapy. However, the eradication rate with quadruple therapy was still insufficient. Consequently, a new therapeutic approach to H. pylori infection in children is needed.