Abstract Background Coronary no-reflow is a potentially lethal complication of percutaneous coronary intervention (PCI). There is a growing body of evidence on how to best prevent this condition by the proper stenting technique and other mechanical measures or adjunctive drug treatments. However, it is still controversial how to tackle coronary no-reflow when it occurs. Purpose We aimed to compare and rank intracoronary agents for acute treatment of coronary no-reflow by considering both indirect and direct evidence from the literature in a network meta-analysis. Methods We searched the databases PubMed, Embase and Central for randomised controlled trials of the acute treatment of coronary no-reflow following primary PCI in patients with ST-elevation myocardial infarction (STEMI) and non-STEMI. Trials with patients suffering from stable angina and/or receiving elective PCI, observational study design and no measure of coronary flow were excluded. Two blinded reviewers independently collected studies, assessed risk of bias with the Cochrane risk of bias tool and extracted data. The primary outcome was a measure of coronary flow immediately following the intervention (TIMI flow grade, TIMI frame count or myocardial bush grade), secondary outcome were major adverse cardiovascular events during follow-up. Pairwise and network meta-analysis were performed using the random-effects model within a frequentist framework. Results 8 studies with a total of 540 participants were identified, including 4 multi-arm studies. This enabled 19 pairwise comparisons of 12 different treatments, all administered via intracoronary route (ADE=adenosine, DIL=diltiazem, DIP=dipyridamole, NIT= nitroglycerin, NPR=nitroprusside, PLA=placebo, TIR=tirofiban, U+V=urokinase combined with verapamil, URA=urapidil, URO=urokinase, VER=verapamil X+T= Xuesaitong combined with tirofiban). Overall, risk of bias in these studies was rated moderate. For graphical representation of the network for the primary outcome, see left panel of the figure. It exhibited a low level of inconsistency and heterogeneity with a global I2 value of 20.9%. Among the different treatments, URA, X+T, and TIR were more effective in re-establishing coronary flow with the caveat that the results of URA depended on one singular trail with a large variance, see right panel of the figure. NIT was even slightly worse than placebo in the primary outcome, the other agents were equivalent with placebo. In terms of major cardiovascular events during follow-up, TIR exhibited a protective effect compared with placebo at borderline statistical significance (OR 0.3843 [95% CI 0.1488; 0.9923]. For URA, data on secondary outcome were not available. Conclusions Urapidil and Tirofiban are potentially effective candidate drugs for larger randomised controlled trials, which are needed to validate the sparse evidence that is available to date on the acute treatment of coronary no-reflow.