BACKGROUND: Drug-coated balloons (DCBs) represent a "leave-nothing-behind" strategy in percutaneous coronary intervention (PCI), particularly for small vessel disease and in-stent restenosis. However, long-term comparative real-world data between paclitaxel- and sirolimus-coated balloons remain limited, and the impact of lesion characteristics on outcomes is not fully understood. OBJECTIVES: This study aimed to evaluate the 2-year clinical outcomes of coronary DCB therapy and compare the performance of sirolimus- and paclitaxel-coated balloons in a real-world cohort. DESIGN: Single-center retrospective cohort study. METHODS: A total of 92 consecutive patients who underwent DCB-based PCI between January 2020 and December 2022 were retrospectively analyzed. Patients were grouped according to DCB type (sirolimus vs paclitaxel). The primary endpoints were restenosis, target lesion revascularization (TLR), and major adverse cardiac events (MACE), defined as a composite of cardiac death, myocardial infarction, and TLR. Secondary outcomes included changes in angina frequency and severity, and selected laboratory parameters. Outcomes were assessed over 24-month follow-up period. RESULTS: The overall 2-year restenosis rate was 13.0%, with TLR occurring in 7.6% of patients, and MACE in 9.8%. Significant improvements in angina frequency and severity were observed at 3 months (both p < 0.001). C-reactive protein (CRP) levels decreased during follow-up (p = 0.01). Patients with diabetes had numerically higher rates of restenosis (15.0% vs 11.0%) and MACE (12.5% vs 9.6%) compared with nondiabetic patients, although differences were not statistically significant. Similarly, sirolimus-coated balloons were associated with lower rates of restenosis (11.7% vs 15.6%) and TLR (6.7% vs 9.4%) compared with paclitaxel-coated balloons, without statistical significance. Larger vessel diameter was associated with an increased risk of restenosis (p = 0.004). CONCLUSION: In this real-world cohort, coronary DCB therapy was associated with acceptable 2-year clinical outcomes and significant symptom improvement. Although sirolimus-coated balloons showed numerically favorable results, no definitive conclusions regarding superiority can be drawn. Larger prospective studies are needed to confirm these findings and to better define optimal patient and lesion selection. TRIAL REGISTRATION: Not applicable. Comparing two types of drug-coated balloons in coronary artery disease: a two-year real-world studyCoronary artery disease is one of the leading causes of heart problems worldwide. It occurs when the blood vessels supplying the heart become narrowed or blocked. One common treatment is a procedure called percutaneous coronary intervention (PCI), which helps restore blood flow. Traditionally, small metal tubes called stents are placed in the artery to keep it open. However, stents remain permanently in the body and may lead to long-term complications in some patients. Drug-coated balloons (DCBs) are a newer treatment option. They deliver medication directly to the artery wall during a short inflation and do not leave any permanent device behind. In this study, we evaluated the outcomes of 92 patients who were treated with DCBs and followed for two years. We compared two commonly used types of drug-coated balloons: one coated with paclitaxel and the other with sirolimus. Overall, the results showed that DCB treatment was safe and effective. Most patients experienced improvement in their symptoms, such as chest pain. The rates of repeat narrowing of the artery and major heart-related events were relatively low. Patients with diabetes had slightly higher event rates, but the differences were not statistically significant. We also found that larger artery size was associated with a higher chance of the artery narrowing again after treatment. This finding suggests that the size and characteristics of the artery may influence how well the treatment works. In summary, drug-coated balloon therapy appears to be a safe and effective option for selected patients with coronary artery disease. Further studies with larger patient groups are needed to better understand which patients benefit the most from this treatment.