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Background: Treating coronary bifurcations remains limited by technical difficulties and suboptimal long-term outcomes, often affecting the side branch (SB). Drug-coated balloon (DCB) in SB treatment could reduce neointimal hyperplasia and the risk for restenosis., Methods: We performed a systematic review of all studies published between January 2000 and February 2018 reporting the outcomes of DCB vs non-coated balloon angioplasty (BA) in the treatment of the SB in coronary bifurcation lesions. Outcomes included SB late lumen loss, SB binary restenosis, target-lesion revascularization (TLR), and major adverse cardiac event (MACE) rate., Results: Four studies with 349 patients were included in the meta-analysis (three randomized controlled trials [RCTs] and one observational study). SB stenting was performed in 7.5% vs 8.6% in the DCB and BA groups, respectively. Angiographic follow-up performed after a mean follow-up of 9.1 ± 2.1 months demonstrated that DCB was associated with lower SB late lumen loss compared with BA (mean difference, -0.19 mm; 95% confidence interval [CI], -0.37 to -0.01; P=.04). There was no difference in the risk of SB binary restenosis (odds ratio [OR], 0.52; 95% CI, 0.18-1.47; P=.22). During a mean follow-up of 15.1 ± 5.8 months, DCB and BA had similar risk of MACE (OR, 0.76; 95% CI, 0.4-1.4; P=.40), and TLR (OR, 0.85; 95% CI, 0.3-2.4; P=.76)., Conclusion: Assessment of DCB for SB treatment of coronary bifurcations is limited by low power due to the small number of patients studied. Use of DCB was associated with lower SB late lumen loss, but this did not translate into improved clinical outcomes.