Background: Microsatellite instability-high (MSI-H) is shown to predict response to the immune checkpoint inhibitors (ICPi). Recently, the FDA granted an accelerated approval for the use of pembrolizumab in any solid tumor and nivolumab in metastatic colorectal cancer in patients with MSI-H. However, the immune-related adverse events (irAEs) exhibit a unique heterogeneous spectrum than conventional chemotherapy adverse drug reactions (ADRs). Underestimating the irAEs could be potentially lethal. Objectives: To evaluate the irAEs; their management, and outcome in MSI-H patients treated with ICPi at the National Center for Cancer Care and Research (NCCCR) in Qatar. Methods: All patients with MSI-H and treated with ICPi at the NCCCR between January 2015 and June 2018 were reviewed retrospectively. Radiologic assessment of irAEs and Naranjo score were used to estimate and confirm the probability of ADRs. Patient demographics, immunotherapy treatment, reported irAEs, and their management were collected. Results: Of the total cohort of patients receiving ICPIs; 9 patients with MSI-H were identified; all received pembrolizumab. 45% (n=4) of the patients were still actively on treatment; 22% (n=2) received only 1 dose then passed away; 22 % (n=2) discontinued because of disease progression; and 11% (n=1) of the patients received 2 cycles as neoadjuvant treatment. To the best of our knowledge, this is the biggest cohort of cancer patients with MSI-H in the Middle East. Calculated Naranjo score was 7 in 45% of the patients (n=4) and 5 in 22 % of patient (n=2), which indicates a probable ADR. 34% of the patients (n=3) did not experience ADRs till the date of data cutoff. 8 irAEs were seen in 67% (n=6) of the patients (Table 1). Based on laboratory or radiologic confirmation, 87.5% (n=7) were irAEs and 12.5% (n=1) was not related to pembrolizumab. Laboratory findings confirmed 25% of the ADRs and radiologic findings confirmed 75% of the ADRs. Of those who developed irARs, 3 patients required a hold of treatment, 1 needed monitoring, and 2 required pharmacologic interventions. There was one patient who received empirical pharmacologic intervention at which evaluation showed no relation to immunotherapy. Conclusion: irAEs can sometimes be unpredictable, rare, and often missed. Frequent monitoring and early management of these suspected or confirmed adverse effects is life saving and should be done in a multidisciplinary approach.