BACKGROUND: The European Association of Urology (EAU), American Urological Association (AUA) and National Comprehensive Cancer Network (NCCN) guidelines (GL) represent key international standards for clinical practice. We assessed the adherence to EAU-AUA- NCCN GL in a large real-world multicenter cohort of patients with Upper Tract Urothelial Carcinoma (UTUC), treated with nephroureterectomy. METHODS: A multicenter retrospective analysis from the ROBUUST (ROBotic surgery for Upper tract Urothelial cancer STudy) registry was performed to assess the region-specific adherence rates to guidelines (GL) for perioperative treatments and their impact on oncological outcomes was evaluated with the Kaplan-Meier method. RESULTS: Out of 2307 patients, excision was the most adopted approach for bladder cuff management world-wide (USA 88.6%, EU 90.5%, Asia 89.8%). Postoperative bladder instillation (intravesical chemotherapy) was implemented in 28.4% of all cases and did not impact bladder recurrence-free survival (log rank P=0.45). Lymphadenectomy (LND) in high-risk disease was underused in both locally advanced (cT3-4: USA 35.8%, EU 46.8%, A 25%) and cN+ stages (USA 41.9%, EU 47.9%, A 43%). LND was not associated with better cancer-specific survival (CSS) across all stages (log rank P≥0.53). Adjuvant chemotherapy (AdCHT) was administered overall in 27.8% of pT2-T4 cases, with a significantly higher adoption in Asia (P=0.03); while in pN+ disease, AdCHT rate was 30.2% and did not convey any advantage in CSS (P=0.58). Retrospective design is the main limitation of the present study. CONCLUSIONS: The present contemporary "real world" data suggests poor adherence to current EAU-AUA guidelines for key indicators of quality care such as perioperative bladder instillation of chemotherapy, performance of LND and administration of adjuvant chemotherapy for advanced disease. These findings highlight the need of improving the implementation of these guideline driven treatment strategies.