Recent paleoethnobotanical approaches in historical archaeology have successfully explored the intersection of plantation foodways, social relations, and the environment in contexts of enslavement, including in the colonial period Caribbean. This article presents an analysis of macrobotanical remains from Estate Cane Garden, a 19th century A.D. plantation hospital in St. Croix, U.S. Virgin Islands. In this study, we demonstrate how enslaved people actively negotiated the adverse conditions of slavery by using plant resources to secure their own well-being, by examining the types of plants found at the hospital, interpreting potential plant use, and by situating the hospital assemblage within a broader Caribbean comparative analysis. Ultimately, we argue for the need for a greater number of paleoethnobotanical studies of historic (16th–19th century) Caribbean sites to develop more robust intersite comparisons in order to reach a more nuanced understanding of the roles of plants in plantation lifeways.