Tithonia tagetiflora Desv. (Asteraceae) is a widespread plant in Vietnam, and the species of Tithonia are known as plants containing many biologically active compounds. However, T. tagetiflora's chemical composition remains mostly unknown. Therefore, we now report the structural elucidation of two new sesquiterpene lactones, 8-angeloyloxy-2,14-epoxygermacra-4,10(1),11(13)-trien-6,12-olide (1) and 6-angeloyloxy-1-hydroxy-3,4-epoxygermacra-9,11(13)-dien-8,12-olide (2), together with three known compounds, including two norisoprenoids, (6S,9S)-vomifoliol or (6R,9R)-vomifoliol (3) and (6S,9S)-roseoside (4), and one glutinane type triterpene, epi-glutinol (5), from the leaves of T. tagetiflora. Their structures are established by 1D and 2D NMR spectroscopy, as well as ESI-MS analysis and comparison with literature data. Copyright © 2013 John Wiley & Sons, Ltd.