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Evaluating performance of the Islamic financial and economic institutions and identifying their mechanisms can help to have a better policy-making in banking system. In this regard, different variables can be considered to measure the profitability of banks. Among these, return on assets as one of factors affecting profitability of banks is influenced by two categories of internal and external variables. This research aims at identifying the factors affecting the return on assets in Islamic banks. Data are collected from 29 Islamic banks in 10 Islamic countries over the period of 2004-2011 and are analyzed by using panel data regression in linear models. The results indicate that among 9 variables included in the model, there is a strong, positive, and significant relationship between degree of investment and return on assets. Moreover, there is a strong, negative, and significant relationship between expenses management ratio and return on assets.