Background and aims: Potassium-Competitive Acid Blockers (P-CABs) have been used in Helicobacter pylori (H. pylori) eradication therapies in recent years. However, the efficacy and safety of P-CABs compared to Proton -Pump Inhibitors (PPIs) in this setting remain controversial. Methods: The efficacy and safety of P-CABs and PPIs for H. pylori eradication were compared in a meta-analysis based on a systematic literature search of major electronic databases for relevant Randomized Controlled Trials (RCTs). Results: Seven studies and 1,168 patients were included. The pooled eradication rate determined by Intention-To -Treat (ITT) analysis was 90.2% for P-CAB-based and 75.5% for PPI-based triple therapy (pooled RR [95% CI] = 1.17 [1.08-1.28], p < 0.001). The Per-Protocol (PP) analysis also demonstrated significant superior-ity of P-CABs (pooled eradication rate = 92.4% vs. 77.8%; pooled RR [95% CI] = 1.14 [1.03-1.26], p < 0.01). In a subgroup evaluation, P-CABs were significantly better than PPIs as a first-line eradication therapy, in both the ITT analysis (pooled eradication rate = 91.8% vs. 76.4%; pooled RR [95% CI] = 1.18 [1.10-1.28], p < 0.0001) and the PP analysis (pooled eradication rate = 93.0% vs. 78.6%; pooled RR [95% CI] = 1.13 [1.02 - 1.26], p < 0.05). However, P-CABs were not superior to PPIs when administered as salvage therapy, as deter-mined in the ITT (75.0% vs. 66.0%, pooled RR [95% CI] = 1.11 [0.69-1.78], p = 0.66) and PP (85.7% vs. 70.0%, pooled RR [95% CI] = 1.20 [0.82-1.75], p = 0.34) analyses. In a subgroup analysis limited to Japanese patients, both the ITT analysis (pooled eradication rate = 89.6% vs. 73.9%; RR [95% CI] = 1.21 [1.14 - 1.29], p < 0.01) and the PP analysis (pooled eradication rate = 92.0% vs. 75.7%; RR [95% CI] = 1.18 [1.06 - 1.32], p < 0.01) showed that P-CABs were significantly superior compared to PPIs as triple eradication therapy. However, in the subgroup analysis of patients from other countries, there was no significant difference in either the ITT analysis (pooled eradication rate = 93.8% vs. 85.2%; RR [95% CI] = 1.10 [0.99-1.22], p = 0.07) or PP analysis (pooled eradication rate = 95.0% vs. 90.8%; RR [95% CI] = 1.05 [0.98-1.14], p = 0.17). The incidence of adverse events associated with the two regimens did not significantly differ (P-CABs vs. PPIs: 33.6% vs. 40.0%; RR [95% CI] = 0.84 [0.71???1.00], p = 0.05). The incidence of serious adverse events and dropout rate due to adverse events also did not differ (p = 0.44 and p = 0.67, respectively). Conclusions: The efficacy of P-CAB-based triple therapy is superior to that of PPI-based triple therapy as a first-line approach to H. pylori eradication, particularly in Japanese patients. As salvage therapy, the efficacy of the two treatments did not significantly differ. The tolerability of P-CAB-based and PPI-based triple therapy was compara-ble, as was the incidence of adverse events.