Background/Aims: As antibiotic resistance increases and new first-line therapies emerge, salvage therapies for <i>Helicobacter pylori</i> (<i>H. pylori</i>) eradication failures are becoming more common and complicated. This study aimed to systematically review overall salvage regimens after previous failure of <i>H. pylori</i> eradication.Materials and Methods: A systematic review of randomized clinical trials evaluating salvage therapies after previous <i>H. pylori</i> eradication failure was performed. A meta-analysis was conducted when an adequate number of studies suitable for grouping was found.Results: Overall, 36 studies with 77 treatment arms were identified, and they were highly heterogeneous regarding previously failed regimens and salvage regimens under comparison. Bismuth quadruple therapy after failure of standard triple therapy showed a pooled intention-to-treat (ITT) eradication rate of 75.5% (95% CI, 71.6~79.1%), and the rates were significantly higher with 14-day therapy than 7-day therapy by 9% (95% CI, 2~15%). Levofloxacin triple therapy after failure of standard triple therapy demonstrated a pooled ITT eradication rate of 73.3% (95% CI, 68.4~77.3%). In direct comparison, the two regimens were not significantly different in eradication rates. No study evaluated salvage regimens after the failure of bismuth or non-bismuth quadruple therapy.Conclusions: The current studies regarding salvage regimens are highly heterogeneous. Bismuth quadruple therapy and levofloxacin triple therapy may be a reliable option after failure of standard triple therapy, but the regional profile of antibiotic resistance should be considered. Further studies are needed for salvage regimens after failure of non-bismuth or bismuth quadruple therapy.