Summary: Background: The search for an optimal interventional treatment strategy in infrapopliteal peripheral artery disease remains in the focus of interest. Whether drug-coated balloons (DCB) might enhance interventional outcomes after crural interventions is a matter of debate, as studies yielded conflicting results on DCB safety and efficacy. Methods: We analyzed a retrospective cohort of 75 infrapopliteal DCB interventions performed at our institution in 68 patients with peripheral artery disease in Rutherford category 3 to 6. Results: Despite a high rate of long complex lesions and multi-vessel disease, freedom from clinically driven target lesions revascularization (TLR) after 365 days was 68%. After six months, healing or significant improvement of the ischemic ulcer was observed in 78% of cases. Accordingly, freedom from major amputation and death after 365 days was 82%. Freedom from major amputation and death was 76.2% of cases in patients with diabetes mellitus as opposed to 91.5% in patients without diabetes mellitus (p=0.049). Conclusions: With this real-world analysis we would like to contribute to the ongoing discussion on the benefit and safety of DCB treatment in below-the-knee interventions.