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Eradication rates with triple therapy (TT) forHelicobacter pyloriinfection have declined to unacceptable levels. Sequential therapy (ST) is a novel treatment that has shown promise in several controlled trials. Our aim was to assess the efficacy of ST in adults and children compared with that of TT by performing a systematic review and meta-analysis.We performed an electronic search of the following: Cochrane Trial Register (until Issue 4, 2008), MEDLINE (1966 to 21 October 2008), EMBASE (1980 to 21 October 2008), and abstracts from the major US, European, and Asian gastroenterology conferences. Randomized controlled trials (RCTs) and controlled clinical trials with a parallel group design comparing the ST with a TT lasting at least 7 days were used.Ten RCTs enrolled 3,006 adult patients and the odds ratio (OR) for eradication ofH. pyloriwith ST compared with TT was 2.99 (95% confidence interval (CI): 2.47–3.62), giving a number needed to treat (NNT) of 6 (95% CI: 5–7) favoring ST. There was no publication bias. The OR for eradication with ST compared with 10-day TT was 2.92 (95% CI: 1.95–4.38), yielding an NNT of 8 (95% CI: 6–12), favoring ST. In patients with clarithromycin resistance, the OR for eradication with ST was 10.21 (95% CI: 3.01–34.58) compared with TT, but the numbers studied are small. Three RCTs enrolled 260 children and adolescents, and the OR for eradication was 1.98 (95% CI: 0.96–4.07). There was no difference in the rate of side effects between the ST and the TT (OR, 1.01; 95% CI: 0.78–1.30).ST appears to be better than TT in the eradication ofH. pylori.This is a promising therapy, but further trials are needed in other European countries and North America before it can be recommended as a first-line treatment.