Background: Compromised tissue perfusion is a significant risk factor for anastomotic leakage after intestinal resection, leading to prolonged hospitalization, risk of recurrence after oncologic resection, and reduced survival. Thus, a tool reducing the risk of leakage is highly warranted. Quantitative indocyanine green angiography (Q-ICG) is a new method that provides surgeons with an objective evaluation of tissue perfusion. In this systematic review, we aimed to determine the optimal methodology for performing Q-ICG. Method: A comprehensive search of the literature was performed following the PRISMA guidelines. The following databases were searched: PubMed, Embase, Scopus, and Cochrane. We included all clinical studies that performed Q-ICG to assess visceral perfusion during gastrointestinal surgery. Bias assessment was performed with the Newcastle Ottawa Scale. Results: A total of 1216 studies were screened, and finally, 13 studies were included. The studies found that intensity parameters (maximum intensity and relative maximum intensity) could not identify patients with anastomotic leakage. In contrast, the inflow parameters (time-to-peak, slope, and t_1/2max) were significantly associated with anastomotic leakage. Only two studies performed intraoperative Q-ICG while the rest performed Q-ICG retrospectively based on video recordings. Studies were heterogeneous in design, Q-ICG parameters, and patient populations. No randomized studies were found, and the level of evidence was generally found to be low to moderate. Conclusion: The results, while heterogenous, all seem to point in the same direction. Fluorescence intensity parameters are unstable and do not reflect clinical endpoints. Instead, inflow parameters are resilient in a clinical setting and superior at reflecting clinical endpoints.