BACKGROUND: Evidence regarding drug-coated balloon (DCB)-only angioplasty in de novo lesions of large vessels is still limited and mainly focused on paclitaxel-coated balloon. We aimed to analyze the safety and efficacy of sirolimus-coated balloon (SCB)-only angioplasty in de novo lesions in large vessels compared to drug-eluting stent (DES). METHODS: In this retrospective, dual-center, case-control study, we enrolled all consecutive patients treated between January 2022 and January 2024 with SCB-only angioplasty in de novo lesion in large vessel (>
2.75 mm) compared to a propensity-score matched contemporary population treated with DES. The primary endpoint was the rate of target lesion revascularization (TLR), while secondary endpoints were cardiac death (CD), target vessel revascularization (TVR), myocardial infarction (MI), and target lesion failure (TLF), defined as a composite of them. RESULTS: The mean age was 70.1 ± 9.8 years in the SCB group (n = 92) and 67.9 ± 9.6 years in the DES group (n = 92) (p = 0.76). The median follow-up was 19.5 ± 12 months in the SCB group and 20.1 ± 13.1 months in the DES group (p = 0.47). TLR occurred in 6.7% of patients in the SCB group and 5.6% in the DES group (p = 0.75). The incidence of MI, TVR, and TLF were similar between the two groups (4.3% vs 3.3%, p = 0.7, 2.2% vs 3.4%, p = 0.65% and 9.8% vs 8.7%, p = 0.79). CD occurred in 4.3% in the SCB group, compared to 3.3% in the DES group (p = 0.70). CONCLUSION: Our study suggests that SCB angioplasty is both safe and effective in the treatment of de novo lesions of large vessels compared with DES.