OBJECTIVE To investigate quadruple therapy with rabeprazole, amoxicillin, levofloxacin and furazolidone for the eradication of Helicobacter pylori (H. pylori) infection. METHODS A total of 147 patients were divided into the experimental treatment group (n = 78) and the standard triple treatment group (n = 69). The experimental treatment group received rabeprazole 20 mg, amoxicillin 1.0 g, levofloxacin 0.2 g and furazolidone 0.1 g, twice daily. The standard triple treatment group received omeprazole 20 mg, amoxicillin 1.0 g and clarithromycin 0.5 g, twice daily. RESULTS One month after treatment, the (13)C urea breath test was carried out to detect H. pylori. The eradication rate using per-protocol analysis was 94.3% in the experimental treatment group and 73% in the standard triple treatment group (P < 0.05), and using intention to test analysis, these figures were 86% and 67% in the two groups, respectively. Side effects were observed in 34 patients, and included mild dizziness, nausea, diarrhea and increased bowel movement. Eleven of the 34 patients needed no treatment for their side effects. CONCLUSIONS Rabeprazole, amoxicillin, levofloxacin and furazolidone quadruple therapy is a safe method for the eradication of H. pylori with high efficacy and good tolerability.