Although various regimens are empirically accepted for Helicobacter pylori eradication, the efficacy might be declined by multiple individual factors. The necessity of a personalized eradication therapy still remains controversial. The aim of the study was to compare tailored therapy with empiric chosen regimens.Databases of PUBMED, EMBASE, and MEDLINE were searched for eligible studies, published up to October 2015. All relevant controlled clinical trials were included. A random-effect model was applied to compare pooled relative risk (RR) with related 95% confidence intervals (CIs).Thirteen controlled clinical trials integrating 3512 participants were assessed. Overall, the pooled eradication rates of tailored groups were higher than those of empiric ones (intention-to-treat: RR = 1.16, 95% CI 1.10–1.22; preprotocol: RR = 1.14, 95% CI 1.08–1.21). In subgroup analysis, tailored therapy was superior to 7-day standard triple therapy (RR = 1.22, 95% CI 1.16–1.29) and bismuth-quadruple therapy (RR = 1.14, 95% CI 1.07–1.22) on eradication rates; first-line tailored therapy achieved higher eradication rates than first-line empirical regimens (pooled RR = 1.18, 95%CI 1.14–1.22), whereas tailored rescue regimen showed no difference with empirical ones (pooled RR = 1.16, 95% CI 0.96–1.39). Moreover, among different tailored designs, susceptibility-guided tailored therapy obtained higher eradication rates than empiric groups, independent of CYP2C19 genotype detection (with CYP: RR = 1.16, 95% CI 1.09–1.23; without CYP: RR = 1.14, 95% CI 1.01–1.28). Both molecular test-based and culture-based tailored groups were better on eradication rates than empiric groups (molecular: RR = 1.23, 95% CI 1.11–1.35; culture: RR = 1.13, 95% CI 1.06–1.20).Compared with empiric chosen treatments, tailored therapy is a better alternative for H pylori eradication.