This research was conducted to identify and analyze some factors that influence the profitability of Syariah Mandiri banks in Indonesia. The study took a sample of Syariah Mandiri banks in 2006-2014 that had previously been eligible for this study. The variabel used in this study is the ratio of ROA (Return on Assets) as a measure of the profitability of Syariah Mandiri banks and BOPO variables, NIM and inflation variables. The analysis used in this study include descriptive analysis and statistical analysis. While the analysis of the data used is the classical assumption test, multiple regression analysis and hypothesis testing. The results showed that there are several variables that significantly influence the profitability of Syariah Mandiri banks. Having explored further, it is evident that the BOPO have signiificant negative effect the profitability of Syariah Mandiri banks. NIM have positive significant effect of Syariah Mandiri banks, while the Inflation variables not influence the profitability of Syariah Mandiri banks. 
Keywords :BOPO, NIM, inflation, ROA, profitability, Syariah Mandiri bank