Background: Radical cystectomy (RC) with urinary diversion is considered the standard treatment for muscle-invasive and selected cases of high-risk non-muscle invasive bladder cancer. As a complex procedure it carries a high risk for complications, especially infectious ones. Orthotopic ileal neobladders (IN) have the highest risk of infectious complications and hospital readmission in comparison to ileal conduits. Unfortunately, the evidence for antibiotic management, including periprocedural prophylaxis and treatment of asymptomatic bacteriuria (ASB) in this special patient cohort is still limited. Furthermore, there is no international consensus on the clinical risk factors that justify intensified antibiotic use, leading to wide practice variability and concerns regarding antimicrobial stewardship.Objective: This Delphi consensus study aims to identify the best antibiotic management, including periprocedural prophylaxis as well as treatment of ASB, and define procedural, patient-related and microbiological risk factors that warrant antibiotic intensified usage in patients with RC and IN and to establish evidence-informed best practice recommendations.Methods: A modified three-round Delphi process will be conducted in accordance with DELPHISTAR guideline. A diverse panel of 30 – 40 international experts in urology, infectious diseases, microbiology, antimicrobial stewardship and medical oncologists will anonymously give recommendations for antibiotic management and evaluate predefined and newly suggested risk factors using a 6-point Likert scale. Consensus will be defined as ≥70% of participants rating an item as highly important (score 5–6) and <15% rating it as unimportant (score 1–2). Items failing to reach consensus in Rounds 1 and 2 will be reevaluated in subsequent rounds.Outcomes: The primary outcomes are consensus-based best practice recommendation for periprocedural antibiotic prophylaxis, antibiotic prophylaxis for catheter removal and definition of ASB as well as antibiotic management of ASB. The secondary outcome will be a consensus-based list of risk factors justifying intensified antibiotic usage in patients with RC and IN. Dissemination: Findings will be submitted for publication in peer-reviewed journals to support global efforts in harmonizing practice and promoting responsible antibiotic use in bladder cancer treatment with RC and IN.