BACKGROUND : Cxbladder diagnostic tests combine genomic information from urinary mRNA with phenotypic information to either rule out low-risk individuals or identify patients at a high risk of urothelial carcinoma (UC). OBJECTIVE : To evaluate the performance of Cxbladder and urine cytology, and Cxbladder's adjudication of atypical cytology and equivocal cystoscopy. METHODS : This is a retrospective analysis of pooled data from three prospective Cxbladder clinical trials and one real-world clinical study. Physicians were blinded to Cxbladder results, and Cxbladder providers were blinded to clinical results. This study analyzed diverse urology practices in the USA, Australia, and New Zealand. A total of 1784 consecutive, prospectively recruited patients with hematuria or previously diagnosed UC provided 852 samples with both local cytology and Cxbladder results; 153 had atypical cytologies and 14 had both atypical cytology and equivocal cystoscopy. UNASSIGNED : Negative predictive value (NPV) and proportion of tumors missed for Cxbladder and local cytology, and evaluation of Cxbladder for adjudicating atypical cytology and equivocal cystoscopy. CONCLUSIONS : Cxbladder ruled out 35% of patients and NPV 97% (95% confidence interval [CI] 94-98%) compared with 93% (95% CI 91-94%) for cytology; Cxbladder missed 8.5% and cytology missed 63% of tumors. UC was diagnosed in 26/153 cases of atypical cytology (17%). Cxbladder correctly adjudicated all these patients including those with both atypical cytology and equivocal cystoscopy; these patients had a positive Cxbladder result and were diagnosed with UC by pathology. The incidence of patients with both atypical cytology and equivocal cystoscopy is low. CONCLUSIONS : Cxbladder correctly adjudicated all patients diagnosed with UC among those with atypical cytology and equivocal cystoscopy, and outperformed cytology for accurately identifying patients who do not have UC. UNASSIGNED : Cxbladder accurately rules out patients who do not have cancer, and adjudicates cytology and cystoscopy with inconclusive results, minimizing the need for patients to undergo further unnecessary tests and procedures.