BACKGROUND: The necessity of antibiotic prophylaxis for postoperative urinary tract infections (UTIs) after transurethral resection of bladder tumours is controversial. This potentially leads to the overuse of antibiotic prophylaxis and rising antimicrobial resistance rates. The objective of this systematic review and meta-analysis is to compare the impact of different antimicrobial prophylaxis schemes versus placebo on the prevention of postoperative UTI and asymptomatic bacteriuria. METHODS: We designed and registered a study protocol for a systematic review and meta-analysis of randomized controlled trials and non-randomized (e.g. cohort, case-control) studies examining any form of antibiotic prophylaxis in patients with transurethral resection of bladder tumours. Literature searches will be conducted in several electronic databases (from inception onwards), including MEDLINE (Ovid), EMBASE (Ovid), and the Cochrane Central Register of Controlled Trials (CENTRAL). Grey literature will be identified through searching conference abstracts. The primary outcome will be postoperative urinary tract infections. The secondary outcome will be asymptomatic bacteriuria. Two reviewers will independently screen all citations, full-text articles, and abstract data. Potential conflicts will be resolved through discussion. The study methodological quality (or bias) will be appraised using appropriate tools (e.g. Risk of Bias 2.0 tool and Newcastle-Ottawa Scale). If feasible, we will conduct random-effects meta-analysis of outcome data. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g. study design, publication year, the setting of the study, and antibiotics regimen). We will also search, identify, and discuss potential risk factors for urinary tract infections following transurethral resection of bladder tumours. This may serve as basis for a scoping review. DISCUSSION: In times of rising antimicrobial resistance rates, sound evidence on the necessity of antibiotic prophylaxis is essential for implementation into guideline recommendations and for decision-making in clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019131733.