The present article describes a series of 21 N-(aryl)-2-thiophen-2-ylacetamides, which were synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis, and the activity expressed as the minimum inhibitory concentration (MIC) in mug/mL. The compounds 2, 3, 7, 8, 11, 12, 15, 16, and 20 exhibited activity between 25 and 100 microg/mL and could be a good start point to find new lead compounds in the fight against multidrug resistant tuberculosis.