The role that banks as key intermediaries play in the modern economy activities is unquestionable, it is admitted that banks remain one of the key financial intermediaries that provide a variety of services in the economy of every state. However, not all financial intermediaries have a significant impact on modern economies, only a stable and profitable banking sector can adequately play the role of financial intermediary in economy. The bank, as an intermediary in the modern economy must be profitable, and this profitability depends on a number of factors that are referred to in this study as determinants of bank profitability. The effect of internal and external determinants of the bank profitability in South Africa is the main focus of this study. It utilized annual time series internal and external data for the period 2001 to 2013. Quantitative approach methodology using secondary data and panel data technique to measure the impact of the determinants was used in the study. The sample consists of nine banks, followed for 12 years and sampled annually. The results for bank-specific consist of four statistically significant variables such as bank size, non-interest income and non-interest expense and credit risk and four non-significant variables (equity capital, loan, saving deposit, fixe term deposit) also the industry-specific consist only one significant variable (market concentration) while macro-economic determinants consist of three non-significant variables (economic growth, inflation, and lending interest rate). In conclusion, the empirical result shows that the bank specific factors are directly controlled by the Management thereby it has a positive correlation to the bank profitability while the industry specific (market concentration) also positively affects the bank profitability. However, the macroeconomic variables which are beyond the scope of management control were non-significant to profitability but show positive sign. Therefore, the variables which are significant affect positively the bank profitability, and the non-significant variables affect the bank profitability negatively. The findings were consistent with mixed results found in prior literature. / Business Management / M. Com. (Business Management)