In Indonesia, since the issuance of the Banking Law and Law no. 23 of 1999 concerning Bank Indonesia as amended by Law no. 3 of 2004 which accommodates Islamic banking, since 1998 the national Islamic banking has developed quite rapidly, both in assets and business activities. This study aims to determine what factors affect Profitability as measured by Return On Assets (ROA) in addition to Mudharabah Financing and Non Performing Financing. The researcher limits the problems that will be discussed only on mudharabah financing and Non Performing Financing (NPF) to Profitability Ratios as measured by Return On Assets (ROA) of Islamic Commercial Banks. The research method in this thesis uses a quantitative approach. The number of samples is 64 data. The samples used are several banks in Islamic commercial banks, namely Bank Muamalat Indonesia, Bank BNI Syariah, Bank Mega Syariah and Bank Syariah Mandiri, the data is taken from 2016-2019 in the form of quarterly data. With secondary data type. The results obtained: Mudharabah financing variable has an effect but not significant on Return On Assets (ROA) with a significance value of 0.586 > 0.05, then accepted. And the Non Performing Financing (NPF) variable has a significant and significant effect on Return On Assets (ROA). obtained significance value is 0.000 < 0.05 then it is rejected. then hypothesis 3 is accepted with a significant value of 0.000 < 0.05 then Mudharabah Financing and Non Performing Financing (NPF) have a simultaneous and significant effect on Return On Assets (ROA).