The subject of this paper is to measure the efficiency of the Macedonian banking sector by applying two approaches: firstly, comparative analysis on the efficiency indicators of the banking sector in the Republic of Macedonia and the countries of Central and Southeastern Europe (CSEE) and secondly, Data Envelopment Analysis (DEA). The aim is to provide directions and guidelines for further strengthening of the Macedonian banking sector. According to the comparative analysis of the efficiency indicators (net interest margin and operating costs) of the Macedonian banking sector and the countries of CSEE, the countries whose banking sector shows lower operating costs are characterized with a higher level of financial deepening and greater degree of financial intermediation. The high interest margins direct towards unsuitable allocation of financial resources and insufficient competitiveness in the domestic banking sector. When applying the DEA approach, it can be stated that the group of large banks marks the highest efficiency within the Macedonian banking sector. The high concentration degree of banking activities within the group of large banks with a leading role in determining the interest rates, results in a rigid interest policy of the banks. In the direction of strengthening the efficiency of the Macedonian banking sector as a whole, the obtained results show that it is necessary for the banks to be further consolidated so as to utilize the advantages of the economies of scale, increase competitiveness, offer a diversified structure of products, invest in new contemporary software solutions that will allow reinforcement of their employees’ productivity and long-term reduction of the operating costs, as well.