BACKGROUNDFew 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 Helicobacter pylori (H. pylori) in Korean patients.AIMTo compare the efficacy and safety of a TR strategy and those of EBQT regimen as first-line eradication therapy for H. pylori.METHODSThis is an open-label, comparative study in which we prospectively enrolled patients over 18 years of age with H. pylori infection and retrospectively reviewed their data. H. pylori-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 H. pylori 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 H. pylori eradication success rate were evaluated and compared between the groups.RESULTSA total of 150 patients were assigned to the TR (n = 50) or EBQT group (n = 100). The first-line eradication rate of H. pylori did not differ between the groups (96.0% vs 95.7%, P = 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 (P < 0.001).CONCLUSIONDPO-PCR-based TR for H. pylori eradication may be equally efficacious, with less treatment-related complications, compared to EBQT in Korea, where clarithromycin resistance is high.