The investigators performed a network meta-analysis of randomized trials comparing the effectiveness of currently available strategies for the treatment of drug-eluting stent (DES) restenosis. Despite the widespread use of DES in patients who undergo percutaneous coronary intervention, the optimal treatment for DES restenosis remains poorly defined. A systematic search of electronic resources was performed. The primary end point was diameter stenosis at follow-up angiography. Seven trials were included, enrolling a total of 1,586 patients with 1,728 restenotic lesions. The following treatment options were found: balloon angioplasty (BA) in 343 patients (19.3%), iopromide-based paclitaxel-eluting balloons (PEB) in 343 (21.6%), sirolimus-eluting stents in 441 (27.8%), paclitaxel-eluting stents in 462 (29.1%), and everolimus-eluting stents in 34 (2.2%). Compared with BA, PEB (−17.74%, 95% credible interval [CI] −25.17% to −11.31%), everolimus-eluting stents (−14.93%, 95% CI −33.47% to 1.16%), paclitaxel-eluting stents (−15.3%, 95% CI −22.96% to −8.35%), and sirolimus-eluting stents (−11.08%, 95% CI −17.89% to −3.4%) had similar reductions in diameter stenosis at follow-up angiography. PEB (85%) and everolimus-eluting stents (68%) had the greatest probabilities for being the best treatment option. Furthermore, PEB were the best treatment in terms of late luminal loss (85%) and binary restenosis (85%). BA had the lowest efficacy with respect to all study end points. In conclusion, in patients with DES restenosis, repeat DES implantation and iopromide-based PEB are valid alternatives. However, PEB had greater angiographic efficacy and therefore should be considered the new benchmark comparator in the treatment of DES restenosis. The use of BA should be discouraged in patients with DES restenosis.