Background: FDA modified the label for the use of 1st-line pembrolizumab or atezolizumab therapy to PD-L1 high cisplatin-ineligible or platinum-ineligible UC patients (pts) regardless of PD-L1 expression. However, the outcomes when using PD1/PD-L1 inhibitors for platinum-ineligible pts are unclear. We conducted a retrospective study to evaluate clinical outcomes with first-line PD1/PD-L1 inhibitors for platinum-ineligible pts with advanced UC in a real-world setting. Methods: We collected data retrospectively from 6 institutions. The following criteria were deemed to render pts platinum-ineligible although physician discretion was also allowed: Cr Cl < 30 ml/min, ECOG-PS 3, Both Cr Cl 30 to < 60 AND ECOG-PS 2. Demographic and clinical variables and outcomes (overall response rate [ORR], overall survival [OS]) were collected. A Cox regression analysis was done to study the association of baseline variables with response and survival. Results: Data were available for 45 pts. Pts received atezolizumab [n = 24], pembrolizumab [n = 11], nivolumab [n = 7] and durvalumab [n = 3]. The mean age was 72.2 (range 45-90) years. The reasons for platinum-ineligibility were: Cr Cl < 30 ml/min (n = 17), ECOG-PS 3 (n = 3), ECOG-PS 2 plus Cr Cl < 60 ml/min (n = 7), elderly with co-morbidities (n = 12), and reason was unavailable for 6 pts. The median OS was 37 weeks (CI 30-80). ORR was 27.3%: Complete response in 3 pts [6.8%], partial response in 9 pts [20.5%], stable disease in 11 pts [25%] and progressive disease in 21 pts [47.7%] and data for 1 patient was unavailable. Toxicity of any grade were seen in 42.2% of pts and Grade ≥3 toxicity in 9 pts’ [20%]. There were no treatment-related deaths. Anemia (HR = 0.75, 95% CI 0.62 - 0.92, P = 0.005) and liver metastasis (HR = 1.17, 95% CI 0.47 - 2.93, P = 0.017) correlated with shorter OS. Conclusions: To our knowledge, this is the 1st report of efficacy and toxicity of PD1/PD-L1 inhibitors as1st-line therapy for platinum ineligible UC. Data appear comparable to those reported previously in unselected cisplatin-ineligible pts receiving pembrolizumab or atezolizumab in phase II trials. Validation is needed in larger datasets and prospective trials.