This study was undertaken with the objective of asserting the significant determinants of microfinance profitability in Sri Lankan microfinance institutions. This study is based on eleven microfinance institutions in Sri Lanka, within the period of 2005-2010, which are practicing microfinance at present. In this study, profitability is measured by profitability and sustainability ratios. Determinants of microfinance profitability are measured by efficiency and productivity, financing structure and portfolio quality ratios.