Despite numerous Helicobacter pylori treatment studies, the optimum regimen(s) for its eradication remain unclear. Our objective was to determine systematically which regimen(s) gave the best pooled eradication rates, by using meta-analysis methodology. A total of 27 studies were identified. Pooled eradication rates for single (18.6%), double (48.2%), and triple therapy (82.3%) were statistically highly different (p < 0.0005). Eradication rates with amoxicillin (23.0%) and bismuth compounds (19.6%) were equivalent. Combined treatment with bismuth+metronidazole was better than bismuth+amoxicillin (55.1% vs. 43.7%, p = 0.049). Triple therapy with bismuth+metronidazole+tetracycline gave a statistically higher eradication rate (94.1%) than bismuth+metronidazole+amoxicillin (73.1%, p < 0.0005). Despite increased side effects with multiple antibiotic regimens, patients tolerated these well, without significant drop-out. The combination of bismuth, metronidazole, and tetracycline gives the best eradication rate, but the optimal doses and duration of treatment have yet to be determined. Further studies are necessary to explore factors such as antibiotic resistance and drug compliance as important factors affecting antibiotic efficacy.