Smyrna was a flourishing economic centre, in which the Greeks played a prominent role. Naturally, after the landing of Greek troops the National Bank began to contemplate opening a branch there.

This move aimed not only to gain profits and new clients but also assist in incorporating Asia Minor in to the Greek state. It was also important that Greek interests be organized in the area, given that economic competition between the allied powers was launched.

The relationship between the National Bank and state institutions in general and with the High Commission in Smyrna (and Aristidis Stergiadis) in particular, gave the opening of a branch there even greater importance. It contributed to the control of the activity of private agents and banking institutions, that were creating monetary chaos through speculation in the exchange market. This role was so intense that the National Bank came to be considered a 'branch of the Greek Administration in Smyrna'. To this function belongs the conduct of the stock-taking of industrial and manufacuring units, of Greek and other interests, that took place in Asia Minor and especially in the wider Smyrna zone under the responsibility of the National Bank.

Apart from this instrumental role, the Smyrna branch was particularly lucrative in its purely banking mission. It competed successfullly with all the other banks active there in this period, and had the largest turnover. The net profits of the period 1919-22 were 7,515,422,50 drachmas.

In August 1922 with the debacle of the front, the clerks of the branch under the head of Th. Themenakis saw to it that the Bank's archive, securities, gold and a great part of the branch's cash were safely transferred to Chios. During the following days, before the entry of the Turks in to Smyrna, a large number of depositors withdrew their monies. After the departure of the staff, Themenakis remained in the city in order to consummate the transfer of the Bank's assets, as well as the merchandise stored in its warehouses. Despite the reassurance of the British and French consuls, persecutions followed, massacres and the burning of the city and Themenakis's intentions were never fulfilled. He himself finally escaped, thanks to the the above consuls.