Background: SG is an antibody drug conjugate (ADC) FDA approved for treatment refractory UC with Response Rate (RR) of 27%. Many patients (pts) receive SG after disease progression (PD) on EV, another ADC commonly used in earlier lines of therapy. In the TROPHY study, 10/113 pts treated with SG received prior EV and RR was similar to that of the entire cohort. We present a real-world experience in pts treated with SG after EV. Methods: In this retrospective analysis, pts with aUC treated with SG following EV at Johns Hopkins were identified. Demographic and treatment details were extracted by chart review. RR [Complete Response (CR) + Partial Response (PR)] with 95% Confidence Interval (95%CI) were compared between pts who did and did not have response to EV and between subgroups of interest using the χ² test. Response to EV was defined as physician-assessed CR or PR. Cox proportional hazard model analysis was used for comparing progression free (PFS) and overall (OS) survival for SG between groups. Results: 23 pts were identified, including 10 (43.5%) females and 19 (82.6%) white. Median age was 71.8 years (range: 46.3, 85.4). Primary tumor location was upper tract for 11 (47.8%) pts, lower tract for 11 (47.8%) and 1 pt had tumor in both sites. 11 (47.8%) pts had liver metastasis present at SG initiation. SG was 3rd line treatment for 5 (21.7%) pts and ≥ 4th line for 18 (78.3%). 4 (17.4%) pts had tumors with variant histology. RR for the entire cohort was 17.4%. Reason for discontinuation was PD in 16 (69.6%) pts and toxicity/functional decline in 7 (30.4%). The table summarizes RR in different subgroups. Median PFS for SG was 2.63 months among EV responders and 1.35 months for non-responders [Hazard Ratio (HR): 0.31, 95%CI: 0.12, 0.83, P = 0.02]. Median OS for SG was 5.36 months in EV responders and 5.78 months in non-responders (HR: 0.82, 95%CI: 0.27, 2.46, P= 0.7). No PFS or OS difference was found between subgroups: Upper vs lower tract primary tumor, liver metastasis presence vs absence, variant histology vs pure UC, estimated glomerular filtration rate (eGFR) ≥ 30 mL/min vs < 30. The small sample precluded multivariable analysis. Conclusions: To our knowledge this is the largest real-world cohort of pts with UC treated with SG post EV. A trend towards improved RR and PFS for SG was noted among EV responders. In our analysis clinical outcomes remained consistently similar across all subgroups, including pts with known poor prognosis risk factors.