Background: Anti-PD1/PD-L1 therapy is standard-of-care for patients with a variety of advanced malignancies. Although clinical trials report a lower incidence of grade 3-4 toxicities than observed with cytotoxic agents, it is imperative that clinicians identify and manage the unique toxicities of these agents. We aimed to identify real-world incidence of immune-related toxicities and management for patients treated with anti-PD1/PD-L1 agents prior to publication of clinical practice guidelines. Methods: Patients enrolled in a Humana Medicare Advantage plan who initiated any anti-PD1/PD-L1 therapy September 1, 2014–February 28, 2018 were identified. NCCN Guidelines for immune-related toxicity were used to determine appropriate pharmacy and medical codes from administrative claims data for toxicity identification and management. ICD-10 codes were examined for patients requiring hospital or ED visits, and HCPCS and NDC codes were used for patients requiring toxicity treatment (eg, corticosteroids, anti-TNFα). Results: 6,005 patients were identified; 39.1% were female, median (IQR) age was 72 years (67–77). The majority (64.7%) had thoracic cancers; 16.3% genitourinary cancers; and 12.8% skin cancers. The median number of anti-PD1/PD-L1 doses received was 4 (2–8). Overall, 62.5% (n=3,751) of patients experienced >1 toxicity with half (n=1,913) requiring an inpatient stay or ED visit, and the other half (n=1,838) receiving outpatient toxicity medication. A similar proportion of patients developed >1 toxicity, regardless of age: <75 years, 62.4% (n=2,416); and 62.5% (n=1,335) >75 years. Systemic corticosteroids were used by 61.3% (n=2,300) of patients that experienced toxicity. The most frequently observed toxicity in this dataset by organ system was cardiovascular (18.5%, n=1,108), which was comprised largely of arrhythmias (13.7%; n=823), and endocrine toxicities (15.8%; n=950), mostly type 2 diabetes (11.9%; n=714). Conclusion: Real-world data from a large Medicare Advantage plan indicate that half of patients receiving anti-PD1/anti-PD-L1 may experience a toxicity resulting in an inpatient stay or ED visit with no difference by age. While attribution of toxicity may be challenging using claims data, the spectrum of immune-related toxicities in the real world may differ from those reported in clinical trials. Future research should evaluate incidence and management of toxicities post-guideline release and monitor changes in site of care for management.