This paper examines the factors that account for the deterioration in the asset quality of Ghanaian banks during a period of financial crises using a unique dataset on 25 banks from 2005 to 2010. Based on system Generalized Method of Moments estimations, we find that the persistence of non-performing loans in addition to loan growth, bank market structure, bank size, inflation, real exchange rate and GDP growth are the significant determinants of banks asset quality in Ghana. The findings have implications for both bank management and regulators in emerging economies.