Introduction: Pembrolizumab and Nivolumab are part of Immune-checkpoint inhibitor (ICI) therapy that have shown marked efficacy in the treatment of different cancers. Drug related immune toxicity is a known and frequent side effect of these medications. At our new cancer care center, we aimed to compare the autoimmune toxicities of these two medications and to explore the predisposing factors leading to these toxicities. Methods: 151 patients treated with Pembrolizumab and/or Nivolumab at a large new cancer care center for primary diagnosis of any cancer from January 2017 to December 2019 were included in the study. Patients were followed for an average duration of 25 to 30 months. Data was compiled using descriptive statistics. Comparative data was analyzed by t-test and chi-square method using strata. Results: The prevalence of new drug related immune toxicity was not significantly different amongst Pembrolizumab group and Nivolumab groups (34.1% vs 28.7%, p= 0.35). Amongst these patients, Pembrolizumab related immune toxicity was significantly more common in patients with underlying autoimmune disease, when compared to Nivolumab (41.3% vs 5.2%, p= 0.007). Hypothyroidism was the most common immune toxicity in Pembrolizumab group (36%, n=9), while immunological rash was a predominant side effect in Nivolumab group (33%, n=6). Combination analysis of both groups showed that endocrine related immune toxicity was the most frequently encountered (18 patients, 41%). In both groups, drug related immune toxicity was more related to female sex (60%) and significantly greater number of patients in Nivolumab group were current smokers (15 vs 5, p= 0.003). Immune related pneumonitis was equally prevalent in both drug groups (4.7% vs 4.5%) with most susceptible period being between 6 months to 1 years after starting immunotherapy (75%). Among patients with pneumonitis, underlying structural lungs disease seems to be a prominent risk factor (75% vs 66%). Conclusion: Pembrolizumab and Nivolumab have comparable toxicity profile with endocrine related side effects being the most common. Immune related drug toxicity remains a significant use limiting side effect of these medications and appears to predominate in patients with underlying autoimmune disease. Larger studies with greater sample size directed at individual immune toxicities might help identify the significant predisposing risk factors leading to these toxic reactions.