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Drug-coated balloons (DCB) have been used to treat de novo small vessel coronary disease (SVD), with promising results and shorter dual antiplatelet therapy (DAPT) duration compared to drug-eluting stents (DES). We compared safety and effectiveness of the two treatments at 1 year.We reviewed 3,613 angioplasty cases retrospectively from 2011 to 2013 and identified 335 patients with SVD treated with device diameter of ≤2.5 mm. DCB-only angioplasty was performed in 172 patients, whereas 163 patients were treated with second-generation DES.DCB patients had smaller reference vessel diameter (2.22 ± 0.30 vs. 2.44 ± 0.19 mm, P 0.001) and received smaller devices (median diameter 2.25 vs. 2.50 mm, P 0.001) compared to the DES group. DES-treated vessels had larger acute lumen gain (1.71 ± 0.48 mm) than DCB (1.00 ± 0.53 mm, P 0.001). Half the patients had diabetes mellitus. While there were more patients presenting with acute coronary syndrome (ACS) in the DCB group (77.9% vs. 62.2%, P = 0.013), they received shorter DAPT (7.4 ± 4.7 vs. 11.8 ± 1.4 months, P 0.001) than the DES group. The 1-year composite major adverse cardiac event rate was 11.6% in the DCB arm and 11.7% in the DES arm (P = 1.000), with target lesion revascularization rate of 5.2% and 3.7%, respectively, (P = 0.601).In this high-risk cohort of patients, DCB-only angioplasty delivered good clinical outcome at 1 year. The results were comparable with DES-treated patients, but had the added benefit of a shorter DAPT regime.