To systematically review the Helicobacter pylori eradication efficacy with ranitidine bismuth citrate (RBC) and two antibiotics, and to conduct a meta-analysis of randomized clinical trials comparing the efficacy of proton pump inhibitor (PPI) vs. RBC with two antibiotics for 1 week. Studies evaluating RBC plus two antibiotics were considered. For the meta-analysis, randomized controlled trials comparing PPI vs. RBC plus two antibiotics for 1 week were included. Electronic and manual bibliographical searches. Assessment of study quality and data extraction: Independently done by two reviewers. 'Intention-to-treat' eradication rate. Meta-analysis was performed, combining the odds ratios (OR) of the individual studies. Subanalysis: Depending on the type of antibiotics and the quality of the studies. Mean H. pylori eradication with 7-day RBC-clarithromycin-amoxicillin, RBC-clarithromycin-nitroimidazole, and RBC-amoxicillin-nitroimidazole was 83%, 86%, and 71%, respectively. The meta-analysis showed comparable efficacy with RBC and PPI when they were combined with clarithromycin and amoxicillin (OR = 1.11; 95% CI = 0.88-1.40), or with amoxicillin and metronidazole (OR = 0.92; 95%CI = 0.60-1.41). However, when comparing PPI vs. RBC plus clarithromycin and a nitroimidazole, higher cure rates with RBC than with PPI were demonstrated (OR = 1.65; 95% CI = 1.15-2.37). The efficacy of RBC and PPI-based triple regimens were comparable when using the clarithromycin-amoxicillin or the amoxicillin-metronidazole combination. However, RBC seems to have a higher efficacy than PPI when clarithromycin and a nitroimidazole are the antibiotics prescribed. Therefore, if one prefers to use the clarithromycin-nitroimidazole regimen, RBC should be used instead of a PPI.