Background: Anastomotic leakage after a colorectal resection results in devastating consequences for patients. Indocyanine green fluorescence angiography is a modality to visualize vascular perfusion at the anastomotic site and can help surgeons decide the viability of the anastomosis. We performed this systematic review and meta-analysis to evaluate the efficacy of indocyanine green fluorescence angiography in decreasing anastomotic leakage. Methods: PubMed, Web of Science, Embase, and the Cochrane Library were searched to identify studies comparing the use of indocyanine green fluorescence angiography versus standard care on rates of anastomotic leakage. Data were pooled with the Mantel-Haenszel method and analyzed based on a random-effects model to estimate the pooled odds ratio and 95% confidence interval. The heterogeneity of studies was evaluated using I 2 statistic. Results: Twenty studies were included in this meta-analysis of 5,498 patients. The pooled estimate of the odds ratio was 0.46 (95% confidence interval 0.34e0.62; P < .00001) favoring indocyanine green fluorescence angiography. The overall anastomotic leak rate was 3.7% (n ¼ 82) in the intervention group and 8.6% (n ¼ 282) in the control group. Indocyanine green fluorescence angiography led to a change in the anastomotic site in 216 (9.7%) patients. Subgroup analyses of anastomotic leakage requiring intervention, patients requiring a low colorectal anastomosis, and prospective studies had a pooled estimate of odds ratio 0.55 (95% confidence interval 0.35e0.89), odds ratio 0.38 (95% confidence interval 0.27e0.54; P < .0001), and odds ratio 0.49 (95% confidence interval 0.30e0.81; P ¼ .005) respectively. Conclusion: The use of indocyanine green fluorescence angiography is associated with a decrease in anastomotic leakage. This association is present in patients with severe anastomotic leakage requiring intervention as well as low colorectal anastomoses.