Background: Checkpoint inhibitors (CPIs) targeting PD-1/PD-L1 and CTLA-4 have revolutionized management of GU malignancies. These agents are associated with a unique subset of toxicities that are immune-mediated, with a broad clinical spectrum that may affect any organ. Patients can also experience ³1 irAE involving multiple organ systems. Individual patient susceptibilities and type of CPI used may influence the incidence and type of irAEs that may develop. Wehypothesize that there are also differences in irAEs based on the histologic malignancy subtype. Methods: We performed a retrospective analysis of all patients with GU malignancies who received CPIs at the University of California Irvine using an outpatient oncology pharmacy database. Data was collected from 1/1/2020 to 6/30/2021. Patients were aged ³18 years and had a diagnosis of urothelial carcinoma (UC), renal cell carcinoma (RCC), prostate adenocarcinoma, or penile squamous cell carcinoma. Patients must have received ³1 dose of a CPI agent including ipilimumab (I), nivolumab (N), pembrolizumab (P), atezolizumab (At), avelumab (Av), durvalumab (D), and cemiplimab (C). Results: A total of 128 patients who received 141 unique CPI regimens were included. Documented irAEs were noted in 50.0% of patients and 18.4% had ³1 irAE. A total of 99 unique irAEs were recorded. In those who experienced irAEs, 92.2% of patients received CPIs in the metastatic setting and 7.8% in the adjuvant setting. In those who experienced irAEs, 12.5% of patients received combination CPIs with I+N, while 87.5% received single-agent CPI. In those who experienced irAEs, 46.8% of patients had UC, 50.0% had RCC, 1.6% had prostate cancer, and 1.6% had penile cancer. In those who experienced irAEs, 24.2% had skin rash or pruritis, 23.2% had endocrinopathies, 14.1% had colitis, 13.1% had other toxicity including arthritis, 12.0% had hepatitis, 3.9% had myositis, 2.9% had pneumonitis, 1.9% had neurologic toxicity including myasthenia gravis and encephalitis, 1.9% had carpal tunnel syndrome, 1.9% had nephritis, and 0.9% had autoimmune thrombocytopenia. Various irAEs for UC and RCC are summarized in Table. Conclusions: In this dataset, there were differences in type and incidence of irAEs in patients with UC and RCC, while the sample size was too small to draw conclusions about patients with prostate and penile cancer. Further investigation is needed involving other solid tumor types, including non-GU malignancies, to definitively answer this question.