Aim: Immune Checkpoint Inhibitors (ICIs) are widely used in Advanced Urothelial Cancer (aUC). However, predicting durable responses to ICIs remains challenging and conventional response criteria may not capture the complexities of immunotherapy-induced responses. Specifically, the occurrence of hyperprogression, characterized by rapid disease progression following ICI initiation, has not been adequately studied in aUC. We aimed to investigate the prevalence, clinical characteristics, and prognostic significance of hyperprogression in patients with aUC treated with ICIs. Methods: In this retrospective study, we included 54 patients with aUC treated with ICI monotherapy. Hyperprogression was defined using two established criteria: hyperprogressive disease (HPD: ?2-fold increase in tumor growth rate before and after ICI initation) and/or fast progression (FP: ?50% increase in disease burden within 12 weeks from ICI initiation). Measurements were based on radiology reports. Central radiology review was also performed when possible. Results: All patients were assessed for FP and 43 for HPD. Central radiology review was performed in 23 cases. HPD was found in 7 cases (16.3%) and FP in 22 (40.7%). There was no association of the development of hyperprogression with baseline characteristics of patients. Median OS for patients with HPD was 11.8 (95% confidence interval [CI]: 3.8-19.6) vs. 17.6 (95% CI: 12.1-42) months for those without (p=0.076). The respective median OS for patients with FP was 10.8 (95% CI: 5.7-17.5) vs. 23.8 (95% CI: 15-52) (p=0.005). Similar results were found after central radiology review. Long-term survival and response to subsequent therapies was observed among patients with hyperprogression on ICIs. Conclusion: Hyperprogression occurs in patients with aUC treated with ICIs. In the absence of predictive tools and specific therapeutic guidance, the occurrence of hyperprogression does not have a defined role in decision making.