The aim of this paper is to explore the potential correlation among operational risk and the profitability of Islamic banks in the MENA region. Different measures for profitability were relied upon in previous studies, however, in this article depend on return on assets and return on equity to measure profitability, and efficiency ratio calculated by operating expenses to total assets to measure operational risk. To achieve this objective, the sample comprises 20 Islamic banks from 12 MENA countries, creating panel data for a period of ten years from 2011 to 2020. The analysis was conducted using fixed effect models. The study will analyze and interpret the findings from two financial performance measures, namely, ROA and ROE to get insights into the banks' overall financial situation and their ability to generate profits from their assets and equity. Using one type of operational risk measured by (efficiency ratio) as an independent variable, along with profitability measures by (ROA and ROE) as dependent variables. These measures had a significant negative impact by the operational risk measured by (efficiency ratio). This means when the operational risk increases, this indicates that the management is not controlling the operations of the bank in the best way and inability or failure of the bank's management to effectively utilize the available resources and assets to generate satisfactory profits. This leads to an increase in the operating expenses and hence a decrease in profitability measures.