Summary Background Levofloxacin triple therapy has been used for the first‐line and second‐line treatment of Helicobacter pylori infection for more than 10 years. Aims To systematically review the efficacy of levofloxacin triple therapy in the first‐ and second‐line treatment, and to assess the time trend and factors that might affect its efficacy. Methods Prospective trials reporting the efficacy of levofloxacin triple therapy in either the first‐line or second‐line treatment of H. pylori infection in adults were searched from the PubMed and Cochrane database from January 2000 to September 2015. Meta‐analysis was performed to calculate the cumulative eradication rate and the efficacies in subgroups. Results Of the 322 articles identified, a total of 4574 patients from 41 trials, including 16 trials in the first‐line treatment and 25 trials in the second‐line treatment were eligible for analysis. The cumulative eradication rate was 77.3% (95% confidence intervals, CI: 74.7–79.6) and was 80.7% (95% CI 77.1–83.7) in the first‐line treatment and 74.5% (95% CI: 70.9–77.8) in the second‐line treatment. The efficacies of levofloxacin triple therapy before 2008, between 2009 and 2011, and after 2012 were 77.4%, 79.6% and 74.8% respectively. The eradication rate was higher when levofloxacin was given once daily (80.6%, 95% CI: 77.1–83.7) than twice daily (73.6%, 95% CI: 69.7–77.2). The efficacy was significantly higher in levofloxacin‐susceptible strains than resistant strains (81.1% vs. 36.3%, risk ratio 2.18, 95% CI: 1.6–3, P < 0.001). Conclusion The efficacy of levofloxacin triple therapy has been lower than 80% in many countries and it is not recommended when the levofloxacin resistance is higher than 5–10%.