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Objective:Helicobacterpylori (H.pylori) eradication remains a challenge with increasing antibiotic resistance.Hybrid therapy has attracted widespread attention because of initial report with good efficacy and safety.However,many issues on hybrid therapy are still unclear such as the eradication efficacy,safety,compliance,influencing factors,correlation with antibiotic resistance,and comparison with other regimens.Therefore,a comprehensive review on the evidence of hybrid therapy for H.pylori infection was conducted.Data Sources:The data used in this review were mainly from PubMed articles published in English up to September 30,2015,searching by the terms ofHelicobacterpylori or H.pylori,and hybrid.Study Selection:Clinical research articles were selected mainly according to their level of relevance to this topic.Results:Totally,1871 patients of 12 studies received hybrid therapy.The eradication rates were 77.6-97.4％ in intention-to-treat and 82.6-99.1％ in per-protocol analyses.Compliance was 93.3-100.0％,overall adverse effects rate was 14.5-67.5％,and discontinued medication rate due to adverse effects was 0-6.7％.H.pylori culture and sensitivity test were performed only in 13.3％ patients.Pooled analysis showed that the eradication rates with dual clarithromycin and metronidazole susceptible,isolated metronidazole or clarithromycin resistance,and dual clarithromycin and metronidazole resistance were 98.5％,97.6％,92.9％,and 80.0％,respectively.Overall,the efficacy,compliance,and safety of hybrid therapy were similar with sequential or concomitant therapy.However,hybrid therapy might be superior to sequential therapy in Asians.Conclusions:Hybrid therapy showed wide differences in the efficacy but consistently good compliance and safety across different regions.Dual clarithromycin and metronidazole resistance were the key factor to efficacy.Hybrid therapy was similar to sequential or concomitant therapy in the efficacy,safety,and compliance.