Abstract Background The usage of drug coated ballons (DCB) in percutaneous coronary interventions (PCI) is rising. Initially applied in in-stent restenosis (ISR), wider clinical applications especially in de novo lesions (DNL) are discussed. Here we aim to assess the pattern of usage as well as the clinical and angiographic outcomes associated with DCB. Methods For this analysis we included all patients treated with DCB during PCI, at a tertiary care centre between 01/2015 and 12/2021. Cath lab results of all patients were screened to assess the DCB indication. Patients were followed up until 09/2022 to assess clinical as well as angiographic complications. Results A total of 7608 interventions were carried out between 2015 and 2021, in 462 (6.1%) a DCB was used. The median follow-up time were 3.1 years (IQR 1.6 to 4.4 years), the median age of our patient population was 66 (IQR 58-75) and 24.7% (n=114) were female. There were 92 of 462 (19.9%) cases including a DNL preparation, 335 (72.5%) cases treating an ISR, in 6 (1.3%) cases both, DNL and ISR were treated, and in 29 (6.3%) cases DCB were used for other reasons (e.g. pre-/ postdilatation in coronary stenting). The mean DCB inflation diameter was significantly higher in ISR with 3.50mm (IQR 3.0-3.5mm) compared to DNL with 2.50mm (2.00-2.50mm, p-value <0.001 ) While the number of DCBs used is rising over time (179 cases [38.7%] in 2015-2018, 283 cases [61.3%] in 2019-2021), the proportion of de novo lesions showed no significant difference (37/179 [20.7%] in 2015-2018, 61/282 [21.6%] in 2019-2021, p-value 0.806, Figure 1). Patients with DCB for ISR had significantly higher rates of arterial hypertension (ISR: 255 [76.1%], DNL: 57 [62.0%], both: 3 [50.0%], other: 20 [69.0%] p value 0.029), hyperlipidaemia (ISR: 228 [68.1%], DNL: 56 [60.9%], both: 2 [33.3%], other: 14 [48.3%], p value 0.041) and previous myocardial infarction (ISR: 231 [69.0%], DNL: 33 [35.9%], both: 2 [33.3%], other: 8 [27.6%], p-value <0.001). When analysing the outcomes, patients with DNL showed lower rates of acute myocardial infarction (8 [8.2%] vs 51 [15.0%]) as well as target lesion (6 [6.1%] vs 56 [16.5%]) and any revascularization (27 [27.6%] vs 122 [35.9%])%]), yet a higher rate of cardiovascular mortality (19 [5.6] vs 9 [9.2%]) during the follow up period compared to patients treated for ISR (Figure 2). Both groups showed a very low rate of target lesion thrombosis within 30 days after PCI (1 [1.0%] vs 1 [0.3%], p-value 0.745). Conclusions The use of DCB in PCIs is increasing, yet as we were able to emphasize with our data, they are primarily used in ISR as well as lesions with a small vessel diameter with favourable outcomes indicated by low event rates. Research should expand beyond small-vessel disease and ISR to assess safety and outcomes of DCB in DNL, larger vessels and bifurcation interventions with one stent to further assess its potential benefits in a wider field of indications.