Background: Almost 50% of patients (pts) with aUC are ineligible for cisplatin-based chemotherapy, which is current first-line treatment. Cisplatin ineligibility is associated with worse outcomes, thus new promising treatment options are an unmet need. EV is an antibody drug conjugate, approved alone or in combination with Pembrolizumab for the treatment of pts with aUC. In the EV 201 study, cisplatin ineligible pts previously treated with checkpoint had a reported response rate (ORR) of 52% to EV alone. This real-world study aims to compare outcomes between cisplatin eligible and ineligible pts treated with EV monotherapy. Methods: This retrospective analysis of pts with aUC treated with EV monotherapy at Johns Hopkins compared investigator-assessed radiographic response to EV, progression free (PFS) and overall (OS) survival in cisplatin eligible vs ineligible pts. Cisplatin eligibility was determined by presence of ≥1 Galsky criteria: Eastern Cooperative Oncology Group Performance Status of ≥2, creatinine clearance < 60 mL/min, hearing loss ≥ Grade 2, neuropathy ≥ Grade 2 or New York Heart Association Class 3 heart failure. Patient demographics and treatment information were extracted by chart review. ORR [Complete Response (CR) + Partial Response (PR)] and Disease Control Rates (DCR) (CR + PR + Stable Disease) were compared between groups, using the χ² test. Multivariable Cox proportional hazard ratios adjusted for gender, race, presence of visceral metastasis and weight were used for comparing PFS and OS between groups, p < 0.05 was considered significant. Results: We identified 46 cisplatin eligible and 32 ineligible pts. The cisplatin eligible group had 36 (78.3%) white and 8 (17.4%) female pts vs 22 (68.8%) white and 12 (37.5%) females in the ineligible group. Mean age was 65.8 vs 76.3 years respectively. 16 (34.8%) cisplatin eligible pts and 12 (37.5%) cisplatin ineligible had upper tract UC. Among cisplatin eligible pts 38 (82.6%) had visceral metastasis at EV initiation vs 29 (90.6%) ineligible. Median PFS [95% Confidence Interval (95% CI)] was 5.7 months (3.8, 7.1) for cisplatin eligible pts and 3.9 (2.9, 5.5) for ineligible [Hazard Ratio (HR): 0.69, 95% CI: 0.41, 1.14, p=0.14]. Median OS (95% CI) was 9.7 (7.2, 12.0) months for cisplatin eligible pts vs 8.8 (5.8, N/A) for ineligible (HR: 0.90, 95%CI: 0.50, 1.62, p=0.7). ORR and DCR were 47.8% (34.1, 61.9) and 65.2% (50.8, 77.3) in cisplatin eligible pts vs 37.5% (22.9, 54.7) and 56.2% (39.3, 71.8) in ineligible pts (p= 0.37 and p=0.42 respectively). Conclusions: In this retrospective real-world study, there was no statistically significant difference in PFS, OS, ORR or DCR between cisplatin eligible and ineligible pts with aUC treated with EV. This is consistent with the excellent outcomes reported in the EV 201 study. Use of EV in aUC eliminates the artificial outcome gap defined by cisplatin eligibility.