Objective To observe the different clinical efficacy of Triple therapy or Quadruple therapy with saccharomyces boulardii in Helicobacter pylori (H. pylori) eradication. Methods 280 H. pylori-positive patients with chronic gastritis or peptic ulcer were randomly divided into four groups: Triple therapy group, Triple therapy plus Saccharomyces boulardii group, Quadruple therapy group, Quadruple therapy plus Saccharomyces boulardii group. The course of treatment lasted 14 days. The outcome of eradication therapy was assessed by 14C-urea breath test performed at 5th week after the end of treatment, 14C-UBT showed negative meant H.pylori was eradicated, otherwise, meant treatment failure. The adverse reactions, compliance and tolerance were compared among four groups. The outcome of 14C-UBT was collected on month 3, 6, 9, 12 and analyzed for the recurrent rates. Results In total, 258 patients completed the treatment and 241 patients were followed up according to the experimental design and completed the recurrent test. The H.pylori eradication rates of Triple therapy group and Quadruple therapy group were significantly lower than that of Triple therapy plus Saccharomyces boulardii group and Quadruple therapy plus Saccharomyces boulardii group (77.8%, 81.7% vs 91.2%, 94.0%, P < 0.05) . The incidence of adverse reactions was significantly higher in Triple therapy group and Quadruple therapy group than Triple therapy plus Saccharomyces boulardii group and Quadruple therapy plus Saccharomyces boulardii group (79.6%, 65.3% vs 32.2%, 30.1%, P< 0.05) . And the accumulative recurrent rate in Triple therapy group and Quadruple therapy group (10.6% ±6.0%, 9.8% ±7.1%) were significantly lower than that in Triple therapy plus Saccharomyces boulardii group and Quadruple therapy plus Saccharomyces boulardii group (2.5% ± 2.2%, 2.4% ± 1.0%), P < 0.05. Conclusion Triple therapy plus Saccharomyces boulardii group and Quadruple therapy plus Saccharomyces boulardii group could improve the H.pylori eradication rate and decrease the recurrent rate, reduce the incidence of antibiotic-associated side effects, so the suitable treatment protocol should be chosen in clinical practice. [ABSTRACT FROM AUTHOR]