Objective To observe the efficacy and safety of rifabutin and furazolidone included triple regimen and minocycline plus furazolidone included quadruple regimen in eradicating refractory H. pylori infection. Methods A total of 146 patients who failed (≥two times) to treat H. pylori with standard anti-H.pylori therapy were selected and divided into esomeprazole, rifabutin and furazolidone treatment group (ERF group, n=74) and esomeprazole, minocycline, furazolidone and bismuth potassium citrate group (EMFB group, n=72). The duration of treatment were both 10 days. Liver and renal functions were examined within three days after therapy. 13C or 14C-urease breath test was performed one month after the medication withdrawal. The patients were followed up once every two weeks during the treatment period. The medication and adverse reactions were recorded in detail. The compliance and rates of adverse events in two groups were compared and analyzed. The eradication rates of the two groups and subgroups were compared by intention-to-treat (ITT) and per-protocol (PP) analyses. The cost-effectiveness of the two groups was evaluated with cost effectiveness analysis (CEA). The cost/effectiveness (C/E) ratio was calculated by PP. Chi-square test and t test were used for statistical analysis. Results There was no significant difference in complicance between ERF group and EMFB group (90.5% vs. 90.3%, P>0.05). There was no significant difference in H. pylori eradication rate between ERF group and EMFB group analyzed by ITT (82.4% vs. 84.7%, P>0.05). Analyzed by PP, there were no significant differences in H. pylori eradication rate between ERF group and EMFB group (91.0% vs. 93.8%), between male subgroup and female subgroup of ERF group (87.9% vs. 94.1%), between subgroup with age less than 60 years and subgroup with age over 60 years of ERF group (89.7% vs. 92.9%), between male subgroup and female subgroup of EMFB group (89.7% vs. 97.2%) and between subgroup with age less than 60 years and subgroup with age over 60 years of EMFB group (93.6% vs. 94.4%) (all P>0.05). There were no statistically significant differences in the rate of adverse events between ERF group and EMFB group (20.3% vs. 22.2%), between male subgroup and female subgroup of ERF group (25.0% vs. 15.8%), between subgroup with age less than 60 years and subgroup with age over 60 years of ERF group (26.2% vs. 12.5%), between male subgroup and female subgroup of EMFB group (19.4% vs. 24.4%) and between subgroup with age less than 60 years and subgroup with age over 60 years of EMFB group (24.5% vs. 15.8%) (all P>0.05). Fixed daily cost, total cost and C/E of ERF group was RMB 59.0 yuan, RMB 590.5 yuan and 648.9, respectively; and the eradication rate was 91.0%(61/67). Fixed daily cost, total cost and C/E of EMFB group was RMB 32.9 yuan, RMB 329.1 yuan and 350.9, respectively; and the eradication rate was 93.8%(61/65). Conclusions Rifabutin and furazolidone included triple regimen and minocycline plus furazolidone included quadruple regimen both have good efficacy, safety and compliance in the eradication of refractory H. pylori infection, and the latter is better. Key words: Rifabutin; Furazolidone; Minocycline; Refractory H. pylori infection; Efficacy