BACKGROUND: Few studies have compared the efficacy and safety profile of a tailored eradication (TR) strategy based on the presence of a 23S ribosomal RNA point mutation with those of empirical bismuth-based quadruple therapy (EBQT) for first-line eradication of () in Korean patients. AIM: To compare the efficacy and safety of a TR strategy and those of EBQT regimen as first-line eradication therapy for . METHODS: This is an open-label, comparative study in which we prospectively enrolled patients over 18 years of age with infection and retrospectively reviewed their data. positive patients diagnosed by rapid urease test, Giemsa staining, or dual priming oligonucleotide polymerase chain reaction (DPO-PCR) were enrolled from May 2016 to September 2018 at Gil Medical Center. Patients with infection received either a TR regimen or the EBQT regimen. In the tailored therapy group that underwent DPO-PCR testing, patients with A2142G and/or A2143G point mutations were treated with a bismuth-containing quadruple regimen. The eradication rate, patient-reported side effect rate, and eradication success rate were evaluated and compared between the groups. RESULTS: A total of 150 patients were assigned to the TR ( = 50) or EBQT group ( = 100). The first-line eradication rate of did not differ between the groups (96.0% 95.7%, = 0.9). The rate of eradication-related side effects for TR was 12.0%, which differed significantly from that of EBQT (43.0%) for first-line treatment ( < 0.001). CONCLUSION: DPO-PCR-based TR for eradication may be equally efficacious, with less treatment-related complications, compared to EBQT in Korea, where clarithromycin resistance is high.