Drosophila gouveai Tidon-Sklorz & Sene and Drosophila antonietae Tidon-Sklorz & Sene (Diptera: Drosophilidae) are two cactophilic sibling species that belong to the Drosophila buzzatii cluster, which comprises seven species living in South America. D. gouveai uses the decaying stems of Cactaceae of the genus Pilosocereus as breeding sites, whereas D. antonietae is mainly associated with Cereus hildmannianus K. Schum. In this article, we investigate the effect that growing in alternative host cacti may have on fitness-related traits, developmental time and viability, relevant for species that live in ephemeral resources. Both species were reared in seminatural media prepared with fermenting tissues of either Pilosocereus machrisis Y. Dawson or C. hildmannianus. Our results show that the specific differences in the traits analyzed are host dependent. Overall, both species performed very well in P. machrisis, whereas survival in C. hildmannianus differed dramatically between species. The viability of D. antonietae was lower than in P. machrisis, whereas D. gouveai barely survived in C. hildmannianus. The results are discussed in relation to biogeographic, morphological, and molecular evidence, and they stress the need to assess the relative significance of host plant use in diversification of the D. buzzatii cluster.