H. pylori infection remains a worldwide spread disease with a definite morbidity and mortality. Unfortunately, no current therapy regimen is able to cure the infection in all treated patients. The efficacy of the widely recommended triple therapies is decreasing, and a novel 10-day sequential therapy has been proposed. Data of 3 previous meta-analyses showed a significantly higher eradication rate following the sequential as compared to the 7-10 days triple therapies. The sequential therapy achieved significantly better results than triple therapies in children, elderly patients, non-ulcer dyspepsia patients, and in those infected with resistant strains towards either clarithromycin or metronidazole. We identified further 10 randomized trials. By pooling data, H. pylori infection was cured in 2,454 (86%; 95% CI: 84.7-87.3) out of 2,853 patients with the sequential therapy and in 2,320 (75.3%; 95% CI: 73.8-76.9) out of 3,079 patients treated with standard triple therapies (p<0.001), corresponding to a number to treat (NNT) of 9. The comparison between the 10-day sequential regimen and 14-day triple therapies deserves further investigations.