After a confused taxonomic history, Prosthechea (Laeliinae, Orchidaceae) has been circumscribed in a broad sense to include species previously placed in Encyclia subg. Osmophytum. However, recent alternative classifications resurrecting old names such as Anacheilium and Hormidium, and proposing new genera such as Euchile, Panarica, Pollardia, and Pseudencyclia were presented, splitting Prosthechea into narrower genera. In this study, we provide a molecular phylogeny of Prosthechea to reassess alternative generic classifications and shed light on evolutionary aspects of this highly diverse Neotropical lineage. Eighty species of Prosthechea s.l. and 12 species of related genera were sampled. Bayesian and maximum parsimony analyses of sequences from three plastid regions (rpl32‐trnL, trnD‐trnT, ycf1) and nrITS were included. Possible conflicts between nuclear and plastid data were assessed with partitioned Bremer support. Ancestral state reconstructions of morphological characters relevant to the genus taxonomy are provided. Our results reinforce the monophyly of the lineage corresponding to a broad circumscription of Prosthechea. The small lineages corresponding to Euchile, Panarica, and Hormidium are monophyletic, whereas the larger Anacheilium, Pollardia, and Pseudencyclia are not monophyletic. Splitting Prosthechea into smaller genera is not supported by our phylogeny, and nonmonophyly also hinders the proposal of a comprehensive infrageneric classification. The phylogenetic relationships recovered reflect better the biogeographic patterns than the previously proposed morphological affinities, pointing to the existence of homoplastic floral traits within the genus. Conflicts between nuclear and plastid partitions were detected, suggesting a possible scenario of reticulate evolution.