Background Studies have shown that irinotecan can improve survival in patients with advanced or recurrent gastric cancer, but the overall benefit of irinotecan in the treatment of advanced or recurrent gastric cancer remains controversial. The aim of this study was to evaluate the benefits and risks of irinotecan for survival in patients with advanced or recurrent gastric cancer. Method We searched PubMed, EmBase, the Cochrane Central Register of Controlled Trials, reference lists of articles, and proceedings of major conferences for relevant clinical trials. We included randomized controlled trials that reported on the efficacy and safety of irinotecan in patients with advanced or recurrent gastric cancer. Outcomes were analyzed by survival rate, objective response rate (ORR), and toxicity. Furthermore, the analysis was further stratified by factors that could affect the treatment effects. Results Eight trials recruiting 1 546 patients with advanced or recurrent gastric cancer were included in the analysis. Overall, irinotecan therapy was associated with a 6% improvement in survival rate, but this difference was not statistically significant (odds ratio (OR) 0.94; 95% confidence interval (95% Cl) 0.70-1.27; P=0.69). However, irinotecan therapy had more frequent ORR than irinotecan-free arm (OR 1.70; 95% CI 1.34-2.17; P <0.001). Furthermore, irinotecan therapy was associated with a clinically and statistically significant increase in the risk for declined hemoglobin, hyponatremia, and diarrhea, but it also protected against thrombocytopenia risk when compared with irinotecan-free therapy. Conclusions There is no evidence to support the use of irinotecan therapy in patients with advanced or recurrent gastric cancer; however, given the significant advantage in ORR irinotecan therapy using combination regimens may be considered for further evaluation in subsets of patients who may benefit from this treatment.