Introduction and objectives <p>The Optilume^® drug-coated balloon (DCB), combining mechanical dilation with localized paclitaxel delivery, is a novel minimally invasive treatment for urethral stricture disease. However, data on its effectiveness across different stricture locations are limited. This study evaluates functional outcomes following treatment for different strictures locations.</p> Materials and methods <p>This retrospective multicenter study included patients treated with Optilume^® DCB for urethral strictures at five European tertiary care referral centers (June 2023 - June 2025). Stricture length was assessed by retrograde urethrography, cystoscopy, or both. Recurrence was defined as any symptomatic stricture requiring treatment. A multivariable logistic regression using preoperative data was developed to predict recurrence requiring treatment.</p> Results <p>In total 86 patients were included across four stricture locations: penile (<i>n</i> = 11, 13%), bulbar/penobulbar (<i>n</i> = 59, 68%), bulbomembranous/membranous (<i>n</i> = 13, 15%) and bladder neck (<i>n</i> = 3, 4%). Postoperative complications within 30 days occurred in 5 (5.8%) patients. Median follow-up duration ranged from 3 to 11 months. Median peak urinary flow increased from 3.5 to 8.8 mL/s preoperatively to 13.5–19 mL/s at 3 months. Stricture-free rates were highest in penile (91%) and bladder neck (100%) strictures, and lower for bulbar (74%) and bulbomembranous/membranous (69%) strictures. On multivariate logistic regression analysis, diabetes was an independent predictor of stricture recurrence (OR = 7.66, 95% CI 1.55–47.12, <i>p</i> = 0.01).</p> Conclusions <p>Optilume^® DCB showed encouraging efficacy and safety across different urethral stricture locations, achieving high stricture-free rates and improved urinary flow. Diabetes independently predicted recurrence, highlighting the value of optimizing modifiable risk factors.</p>