Endoscopic variceal ligation (EVL) is often recommended as an effective method for the treatment of esophageal varices, despite the important tendency of variceal recurrence. Recent studies indicate that combining EVL with argon plasma coagulation (APC) may be a more effective therapy than ligation alone. To investigate these findings, we carried out a systematic review and meta-analysis to compare the safety and efficacy of EVL combined with APC versus ligation alone for the secondary prophylaxis of esophageal variceal hemorrhage. All studies were searched through PubMed, the Cochrane Library, and Science Direct. The outcome measures were relative risk (RR) or risk difference with 95% confidence intervals (CIs) for dichotomous data and standardized mean difference for continuous data. Heterogeneity was calculated using the χ and the I-tests. Two investigators independently identified four randomized-controlled trials included in the research. The variceal recurrence rate was significantly lower in the combined therapy group (RR=0.19, 95% CI: 0.09-0.41, P=0.000). The bleeding recurrence and mortalities in the two groups showed no significant differences (RR=0.29, 95% CI: 0.08-1.04, P=0.058; risk difference=-0.02, 95% CI: -0.08-0.04, P=0.576, respectively). Although the pyrexia incidence rate was significantly higher in the combined group (RR=3.42, 95% CI: 1.56-7.48, P=0.002), there was intertrial heterogeneity (I=52.5%, P=0.097). EVL combined with APC is superior to ligation alone for endoscopic variceal recurrence without severe adverse events in secondary prophylaxis against esophageal variceal bleeding. More high-quality studies are needed to strengthen this conclusion.