Background: Dual stenting technique (DST) is still mandatory for some true bifurcation lesions (BLs), but drug-coated balloon (DCB) alone may offer a new optional treatment with the potential benefits of fewer implants. However, procedural safety presents a concern when using DCB-only to treat true BLs. This study sought to explore the safety and efficacy of the DCB-only strategy for the treatment of true BLs. Methods: Sixty patients with TBLs were randomly assigned to be treated by a DCB-based strategy or DST-based strategy. All patients received angiographic follow-up scheduled after one-year and staged clinical follow-up. The primary endpoint was the one-year late lumen loss (LLL) and cumulative major cardiac adverse events (MACEs) composed of cardiac death (CD), target vessel myocardial infarction (TVMI), target lesion thrombosis (TVT), or target vessel/lesion revascularization (TLR/TVR). The secondary endpoint was the one-year minimal lumen diameter (MLD), diameter stenosis percentage (DSP) or binary restenosis (BRS), and each MACE component. Results: The baseline clinical and lesioncharacteristics were comparable with similar proportions (20.0% vs. 23.3%, p = 1.000) of the complex BLs between the two groups. At the one-year follow-up, LLL was significantly lower in the DCB-based group (main-vessel: 0.05 \pm 0.24 mm vs. 0.25 \pm 0.35 mm, p = 0.013; side-branch: –0.02 \pm 0.19 mm vs. 0.11 \pm 0.15 mm, p = 0.005). MLD, DSP and TLR/TVR were comparable between the groups. The one-year cumulative MACE, all driven by TLR/TVR (6.7% vs. 13.3%, p = 0.667), was low and similar without CD, TVMI or TVT in both groups. Conclusions: Compared to the DST strategy, the DCB- based strategy may be safe and effective in treatment of the selected true BLs. Clinical Trial Registration: Clinical registration number is ChiCTR1900024914.